Cancer.Net Podcast

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In the Research Round Up series, ASCO experts and members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's episode, our guests will discuss new research in head and neck cancer, brain tumors, and health equity that was presented at the 2022 ASCO Annual Meeting, held June 3-7 in Chicago, Illinois.

First, Dr. Cristina Rodriguez will discuss 2 studies on new treatment options for locally advanced head and neck cancer.

Dr. Rodriguez is a medical oncologist at Seattle Cancer Care Alliance, an Associate Professor in the Division of Medical Oncology at the University of Washington, and an Associate Member for solid tumor clinical research at the Fred Hutchinson Cancer Research Center. She is also the Cancer.Net Associate Editor for Head and Neck Cancers.

You can view Dr. Rodriguez's disclosures at Cancer.Net.

Dr. Rodriguez: Hello. My name is Christina Rodriguez. I'm a medical oncologist with a clinical and research focus on head and neck cancer. And today I'm going to discuss research on head and neck cancer that was presented at the most recent 2022 ASCO Annual Meeting. I don't have any relationship to disclose that pertains to the research that I will talk about today. I'd like to discuss 2 abstracts that I thought were practice changing or practice affirming that really addresses some of the key questions that patients and doctors like me have about the treatment of patients with head and neck cancer. So, as you know, most patients with head and neck cancer present with typically locally advanced disease, and most head and neck cancer patients are treated with the intent of curing them most of the time with the use of radiation either as the main treatment or after surgery. And many clinical trials have shown that when we add a chemotherapy called cisplatin to radiation, we improve curative outcomes for patients.

But the first abstract that I will talk about, abstract 6003, asks the question "What do we do for patients who are not candidates for cisplatin chemotherapy?" And we know that a significant proportion of our patients will have other medical problems that could make it difficult for us to give chemotherapy and often will result in complications or more toxicity or in side effects for patients. This clinical trial was carried out in India, and it compared radiation alone for patients with head and neck cancer versus radiation given with a non-cisplatin chemotherapy called docetaxel. What's unique about this clinical trial is that it's specifically focused on patients who were not candidates for cisplatin chemotherapy, something that really hasn't been done for this population. Interestingly enough, they found that when we give docetaxel with radiation in these patients, we find that they do better, they live longer, and they feel better based on quality-of-life questionnaires.

So I will say that this study, abstract 6003, tells us that even in patients who are not candidates for cisplatin to be given with radiation, there is an alternative treatment that we can use, such as docetaxel given with radiation, that might still improve patient's cure rates for their head and neck cancer.

The second study that I think was another interesting study was a clinical trial that asked the question, "Can we give cisplatin in an alternative manner for patients who are undergoing definitive radiation treatment as their main treatment for head and neck cancer?" Like I mentioned, the clinical trials that led to the use of chemoradiation as a standard use cisplatin given in larger doses every 3 weeks, but there's been concern about how well that approach is tolerated by patients. So this particular clinical trial compared patients receiving radiation as curative intense therapy for head and neck cancer with either the cisplatin given every 3 weeks or the cisplatin given at a lower dose once a week.

It's important to know that this trial was done in India, where the population is pretty different from what we see in the United States. These are mostly patients who have HPV-negative cancers, mostly cancers acquired through exposures like tobacco and alcohol. And what they found was that these 2 groups of patients had very similar outcomes. In other words, there didn't seem to be a reduction in the rates of cure when we give chemotherapy every week versus every 3 weeks. And interestingly enough, it looked like from a toxicity or side effect standpoint, the every week seems to be a little bit better tolerated. Patients who got the treatment every 3 weeks also had less need for hospitalization or IV fluids and less utilization of health care resources.

I think this is a very interesting finding because it really provides us with what we call high-level data that the weekly administration can work. I think it's important to recognize that the population that it studied for this particular clinical trial really was more an HPV-negative population. That's important to know because the standards for HPV-positive head and neck cancer are generated from larger trials that use cisplatin every 3 weeks. But we are continuing to study this question, and there's actually a large NRG study, HN009, that is asking that question both for the HPV- positive and HPV- negative population. So we are, I think, making strides in terms of asking the questions that allow our patients not only to receive treatment that is highly efficacious but also that limits side effects and toxicity. I will also mention that these trials were completed during the COVID-19 pandemic, which tells you that the dedication of these researchers to complete something like this in such a challenging time is to be commended. That's all I have to say, and thank you for listening to this brief summary of new research in head and neck cancer from the ASCO 2022 Annual Meeting.

ASCO: Thank you, Dr. Rodriguez.

Next, Dr. Glenn Lesser will discuss 3 studies that looked at new treatments for different types of brain tumors.

Dr. Lesser is the inaugural Louise McMichael Miracle Professor and Associate Chief in the section on Hematology and Oncology in the Department of Internal Medicine at Wake Forest Health. He is also the Cancer.Net Associate Editor for Central Nervous System Tumors.

You can view Dr. Lesser's disclosures at Cancer.Net.

Dr. Lesser: Hello. My name is Glenn Lesser, and I'm a professor of medical oncology and the director of medical neuro-oncology at the Wake Forest Baptist Comprehensive Cancer Center in Winston-Salem, North Carolina. I'm also the editor of the brain tumor section for ASCO's Cancer.Net. And today, I would like to briefly discuss several clinically relevant research studies involving patients with brain tumors that were presented at this year's ASCO Scientific Program. Of note, I have no disclosures or relationships relevant to the abstracts I'll be discussing today.

The first presentation to talk about is a late-breaking abstract presented by Dr. Eric Bouffet, who described the results of a phase II trial of 2 targeted anticancer agents, dabrafenib and trametinib, in pediatric patients with a kind of brain tumor called a low-grade glioma, which harbored something called a BRAF V600E mutation in their tumor DNA. By way of background, gliomas account for about 45% of all pediatric brain tumors, and the majority of these gliomas are low-grade, which include World Health Organization grade 1 and 2 tumors. Common types of pediatric low-grade gliomas include pilocytic astrocytomas, gangliogliomas, and low-grade gliomas that are not otherwise specified. Now, mutations in the BRAF gene are common in certain kinds of cancers, particularly melanoma, and novel oral targeted therapies have been developed to effectively treat these tumors by targeting this mutant BRAF gene. A particular mutation in this gene called a V600E mutation occurs in about 15% to 20% of pediatric low-grade gliomas. The presence of this mutation is thought to lead to an increased risk of progression to a higher grade or a more malignant glioma in these patients, and these mutations in their tumors also predict a less favorable response to chemotherapy.

In adults, recent studies in patients with malignant gliomas, papillary craniopharyngiomas, and melanomas containing V600E mutations have shown excellent results, with 1one of several similar 2-drug combinations that target both the V600E mutation and a second pathway that cells use to escape from this BRAF blockade. Now, early pediatric data suggested that one of these pairs of drugs, the combination of dabrafenib and trametinib, was safe and tolerable and had the ability to effectively treat patients whose tumors had the V600E mutation. So with that as background, this study was started and enrolled patients from 12 months to 18 years of age who had a low-grade glioma that contained a BRAF V600E mutation. And it randomized them to receive either the combination of dabrafenib and trametinib, or an older, standard cytotoxic chemotherapy regimen consisting of carboplatin and vincristine. Importantly, these patients were newly diagnosed, and this was the first systemic treatment they got, following their surgery or biopsy. 110 patients were enrolled, with 73 given the new targeted therapy combination and 37 receiving the standard combination. The most common types of tumors that the patients enrolled on this study had included pilocytic astrocytoma, ganglioglioma, and low-grade glioma.

The results of this trial were that the patients who received the newer combination, targeted treatment of dabrafenib and trametinib, did substantially better than those who received standard, older cytotoxic chemotherapy. Their overall response rate - that's defined as a complete or partial disappearance of the tumor on MRI scan - was 47% versus 11% in the control arm. When patients who had stable disease by MRI were included, 86% of those on the new combination versus 46% of those patients treated with the older chemotherapy had the so-called best clinical response. Now, a large number of patients responding to dabrafenib and trametinib, remain on treatment and are receiving these drugs with an ongoing imaging and clinical response at the time of this report. Patients receiving the new combination had a median or average progression-free survival of 20 months versus about 7.4 months with the older, standard chemotherapy.

The investigators conducting this study also had patients fill out a variety of questionnaires to assess their quality of life while on treatment. Once again, the patients who received dabrafenib and trametinib, on average, experienced an improved quality of life in contrast to those on standard chemo who, on average, had a worse quality of life. The new treatment was also well-tolerated with fewer serious adverse events or side effects when compared with standard chemotherapy. And these side effects were no different than what has been seen in patients without brain tumors who have been treated with this combination, including fevers, headaches, fatigue, skin changes, and lower blood counts. The authors appropriately suggested that these findings demonstrate the importance of molecular testing of these pediatric low-grade glioma tumors at the time of diagnosis and that this combination of dabrafenib and trametinib is a new potential standard of care in those patients who have the BRAF V600E mutant, low-grade tumors. Of note, liquid formulations of these drugs have been developed for those pediatric patients who are unable to swallow capsules or tablets.

The second presentation at ASCO highlighted the continued importance of prospective randomized clinical trials in patients with malignant brain tumors. Dr. Jann Sarkaria from the Mayo Clinic presented the long-awaited results of the Alliance for Clinical Trials in Oncology cooperative group phase II/III study of a PARP inhibitor or placebo added to standard temozolomide and radiation in adult patients with newly- diagnosed glioblastoma, and in addition, glioblastomas that had specific molecular finding called MGMT promoter methylation. This change to the DNA of the tumors prevents the MGMT DNA repair enzyme from being made in the tumors and leads to a better outcome with temozolomide treatment. Some very elegant laboratory science had suggested that adding a type of drug called a PARP inhibitor, which also causes defects in DNA repair, could lead to improved killing of glioblastoma tumor cells. So patients with newly- diagnosed glioblastomas, which had MGMT promoter methylation on genomic analysis, were enrolled on this study between December of 2014 and October of 2018. The study was conducted in 2 phases separated by a pre-planned pause after the first group of patients were enrolled, which was the phase II part of the study. This was done in order to allow a preliminary analysis of the outcomes of the treatment arms to make sure that there was a signal of activity that justified moving on to test this treatment in a larger number of patients, the so-called phase III part of the trial. This trial design hopes to minimize the number of patients treated with an inactive drug and save years of drug development time by avoiding large trials that go on for a long time with what turns out to be ineffective drugs.

For this trial, 447 patients were eventually treated on this trial. Despite the convincing laboratory evidence and early, promising clinical results that led to the trial moving to the second or phase III portion, the final results showed no statistically significant difference in progression-free or overall survival between the 2 arms, that is, those treated with a PARP inhibitor, and those treated with placebo. I personally was very excited about this study and had hoped that the long wait to hear the results indicated that something good was happening. In addition, several of my patients who were treated on the study did exceedingly well, so I, incorrectly, it turns out, expected positive results from the trial. These negative results are a stark reminder of why we spend lots of time and money and energy performing well-designed clinical trials to determine appropriate treatment strategies for our patients, rather than relying on expert opinion or 1 institution's published experience. This approach turns out to be the best way to fairly test treatment strategies and establish new therapeutic approaches which are truly effective.

A final, interesting abstract that was presented at a poster discussion session at ASCO was from the group with the University of Pennsylvania in Philadelphia, and it dealt with the risk of bleeding in patients with brain tumors who had blood clots and were then treated with a newer class of blood thinners or anticoagulants called direct oral anticoagulants, or DOACs for short. It's been known for over 100 years that a variety of types of cancer cause patients to be hypercoagulable, that is, to be predisposed to developing blood clots throughout the venous system. Patients with malignant brain tumors have the highest incidence of all tumors of developing blood clots, which typically occur in the legs, called deep venous thrombosis or DVTs, or in the lungs, called pulmonary emboli or PEs. These clots can lead to a variety of severe and debilitating symptoms, including leg pain, swelling, shortness of breath, heart strain, and even death. For the past 2 to 3 decades, affected patients have typically been treated with a class of medications called low-molecular-weight heparins, which need to be injected under the skin once or twice daily. Over the past decade, a new class of oral anticoagulants called DOACs have generally replaced low-molecular-weight heparins as the primary method of treatment for patients with and without cancer who develop venous blood clots because of their safety, ease of administration, and a lack of requirement for regular blood tests or monitoring. However, little, if any, data has been available to determine the safety of these agents in patients with brain tumors and blood clots, a situation where bleeding into the brain or the brain tumor as a side effect of the anticoagulant could be catastrophic.

In fact, this potential risk led to the exclusion of patients with brain tumors from several of the large trials which established the safety of the DOACs. Despite the absence of evidence, the DOACs are now pretty broadly used in brain tumor patients for the reasons described above. So this abstract described a cohort of patients with glioblastoma who developed venous blood clots between 2014 and 2021 while under treatment at Penn. The authors reviewed the medical record to determine the relative efficacy or effectiveness and the toxicity or side effects experienced by patients treated with the low-molecular-weight heparins and with the DOACs, including the rates of bleeding into the brain or the brain tumor. 121 patients were identified who fit these criteria, and the cumulative incidence of clinically significant intracranial hemorrhage, that is, bleeding into the brain or the brain tumor, by 30 days after starting the drugs, was minimal and similar in the 2 groups. When measured at 6 months, 24% of the patients in the low-molecular-weight heparin group had developed intracranial bleeding, and 4 of those patients had died from this bleeding, while none of the 32 patients in the DOAC group experienced this complication. Thus, these investigators felt that their data suggested that there was a lower incidence of clinically important intracranial hemorrhage or bleeding in patients with glioblastoma and venous blood clots who were treated with DOACs as compared to low-molecular-weight heparin. They went on to suggest that the use of DOACs was a safe alternative in patients with glioblastoma. Now clearly, either a prospective trial, a larger trial, or additional retrospective evaluations with a larger number of patients are needed to prove the safety of this approach. But this data is pretty comforting, as the use of these agents is now widespread in patients with high-grade gliomas.

The ease of administration of a pill once or twice a day, as compared with potentially lifelong injections once or twice a day, is a major quality of life advantage for our patients. Thank you for listening to this brief summary of new research in neuro-oncology from the 2022 ASCO Annual Meeting.

ASCO: Thank you, Dr. Lesser.

Finally, Dr. Manali Patel discusses new research focused on reducing disparities in cancer care.

Dr. Patel is a medical oncologist and Assistant Professor of Medicine at Stanford University. She is also the Cancer.Net Associate Editor for Health Equity.

You can view Dr. Patel's disclosures at Cancer.Net.

Dr. Patel: Today I have the privilege of discussing several really exciting research abstracts that were presented at the 2022 ASCO Annual Meeting. My name is Manali Patel. I'm a thoracic oncologist, meaning I take care of patients and try to provide good care delivery for patients with lung cancer. And I also am a researcher focused on health equity. I have no relevant disclosures for any of the studies that I will be presenting today with the exception of one that I was leading.

And there were several wonderful abstracts that were presented on describing disparities and the ongoing state of disparities continuing within cancer care delivery. What I was particularly struck by were many of the abstracts that I'm presenting this morning and this podcast that really focus on what we can do as a nation and what we can do individually in our clinics to try to move towards action to overcoming these inequities. The first abstract I want to present was looking at how the Affordable Care Act and changes in the Affordable Care Act led to differences in mortality or deaths by race and ethnicity following the enactment in California. And this particular study looked at greater than 150,000 people who were diagnosed with breast cancer, colorectal cancer, and cervical cancer. And they evaluated death rates from these cancers both before and after the implementation of the Affordable Care Act. And what they found was that the cancer death rates for everyone was much lower after the Affordable Care Act was passed, but specifically for individuals who had self-identified as Hispanic ethnicity, who also identified as Black and who identified as White. And so what this abstract showed me was that at a larger level and a macro level, our policies that are enforced at the national level really do play a role in terms of how we can overcome disparities in cancer.

Our group, as I mentioned before, has worked on really trying to integrate community health workers into care. So this abstract paired with local union organizations in Chicago and in Atlantic City to try to help individuals who self-identified as having been from families that were from low-income households and racial and ethnic minorities to communicate their goals and their preferences for care and to also better their relationships with their clinicians as well as to describe their symptoms. And what we found in this randomized trial was that for individuals who received this community health advocate who helped them to better engage with their clinician and who also helped them to describe the symptoms that they were experiencing as well as receive community resources such as food boxes if they were food insecure or be connected to household agencies if they were having difficulties with housing, we found a significant improvement in quality of life, but we also found reductions in the use of the hospital unnecessarily. We also found that this translated into reductions in total cost of care, thereby reducing the amount of out-of-pocket costs these individuals were spending on their cancer care.

One of the other abstracts that I thought really was reflective of the many different ways that we can move towards action was an abstract which looked at during the pandemic, trying to reduce the number of times people need to come in for mammograms, their biopsies, and then any further testing that they needed after their biopsy. And this particular study evaluated what was called a same-day biopsy service, which layered on a same-day mammogram reading program. So at this particular institution, they had already implemented when you came in to get your mammogram as a woman or a man, you would have a read on the same day. So you did not have to wait to find out what your results were. And what they did further to push better care was that they layered on on that same day you could get your biopsy. So almost a one-stop shop. And what they found was that for everyone, regardless of race and ethnicity, the time to biopsies decreased by almost half. And the median days, for example, from an abnormal mammogram to obtaining a biopsy, meaning a sample of that tissue, that it decreased from 10 days median to 5 days. And particular patient populations did much better. And so they were able to show that when you do interventions that move the care to provide better care for everyone, everyone benefits, but particularly our patient populations who identify as racial and ethnic minorities who were more likely to experience delays in care, they also received some benefit from this intervention.

The last study I want to highlight is work which looked at how to improve specialized services for people who would otherwise not receive those. And this particular study looked at stem cell transplantation for people with blood cancers. And what they found was that these services are often only offered in very tertiary centers, so places that may not be as accessible, large institutions that a lot of people may not have access to receiving care. So what they did was they partnered with this large academic institution so that they could build a pathway for individuals who would otherwise not get stem cell transplantation so that they could have access to those services. And it was really a multipronged approach where they not only educated the clinicians in the community practice about the effort, but they also educated the institution-level clinicians about the effort. They also provided shared medical records, which oftentimes in practice, we don't share our medical records with other clinics. And what they were able to do was to convince these clinics and the institution, let's share the medical records so that then you can have access to seeing what's happening for patients that are diagnosed in the community. And then that way we can both document, we can both have access in the community as well as in the institution where they're receiving the specialized service so that there's better communication. They also provided a navigator for each patient that would help each patient to identify any sort of barriers that they may experience to receiving stem cell transplantation. And then they offered telemedicine, which allowed for individuals to receive specialized services in the comforts of their own home without having to travel after the stem cell transplantation had occurred. And what they found was that usually in the institution, most individuals were more affluent. So they had higher levels of socioeconomic status. But after the intervention, individuals that were referred from this community clinic made it such that the affluence really decreased so that it was showing that people who wouldn't otherwise have access, who had identified as having low income, were now able to receive those services and had been receiving transplantation.

I think that these studies really do move us towards a new paradigm of taking action on the many disparities that we know continue to happen. I really appreciate you all for listening to this brief summary of the new research on health equity from the 2022 ASCO Annual Meeting, and I hope to see you next year.

ASCO: Thank you, Dr. Patel.

You can find more research from recent scientific meetings at www.cancer.net.

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ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

Brielle Gregory Collins: Hi, everyone. I'm Brielle Gregory Collins, a member of the Cancer.Net content team, and I'll be your host for today's Cancer.Net podcast. Cancer.Net is the patient information website of ASCO, the American Society of Clinical Oncology. Today we're going to be talking about coping with the mental and emotional challenges of cancer through exercise. Our guests today are Dr. Sheila Lahijani and Sami Mansfield. Dr. Lahijani is an associate clinical professor of psychiatry and behavioral sciences at the Stanford University School of Medicine and the medical director of the Stanford Cancer Center Psychosocial Oncology Program. Dr. Lahijani is also an advisory panelist on the Cancer.Net Editorial Board. Thanks for joining us today, Dr. Lahijani.

Dr. Sheila Lahijani: It's truly my pleasure to be here today, Brielle, with all of you.

Brielle Gregory Collins: Thank you. Ms. Mansfield is the founder of Cancer Wellness for Life and the director of Oncology Wellness for the Sarah Cannon Cancer Institute at HCA Midwest Health. Thanks for joining us today, Ms. Mansfield.

Sami Mansfield: Thanks, everybody, for having me. Excited to be here as well.

Brielle Gregory Collins: Before we begin, we should mention that Dr. Lahijani and Ms. Mansfield do not have any relationships to disclose related to this podcast, but you can find their full disclosure statements on Cancer.Net. Now to start, Dr. Lahijani, how can a cancer diagnosis impact a person's mental and emotional well-being?

Dr. Sheila Lahijani: Thanks for asking this question, Brielle. Usually, when people want to know the answer to this, what I preface it by saying is that there is a spectrum of responses. Many people find themselves to be quite distressed because cancer continues to have quite a lot of stigma, both in this country and as well as internationally. People oftentimes associate it with feelings of despair, anxiety, and helplessness. Having said that, many of these responses and reactions are normal. Some people can progress to have many more significant emotional responses and reactions that can become more disruptive to their lives and to the roles that they play a part in. We really try to meet patients where they're at to better understand how they've previously coped with past life challenges and/or traumas and to identify what strengths they have, what coping mechanisms they have to help them manage the distress associated with cancer. There are patients who also have a history of past psychiatric diagnoses and problems, in which case getting diagnosed with cancer and undergoing cancer treatment can cause a lot more difficulty. So each person is different. There are a lot of, quote-unquote, "normal" reactions, responses and reactions, that we as providers do validate and reflect back to the patients. And then there are those that can cause many more problems, and those are the ones we really need to address.

Brielle Gregory Collins: Okay. And getting into some of those problems, what are some of the most common mental and emotional challenges that people face during cancer?

Dr. Sheila Lahijani: The majority of people feel very anxious. And I've shared this with others and share this with my patients: being anxious means something. It means that you care about something. You care about yourself. You care about your life. You care about people in your life. And so it's a sign. It's something that needs to be tended to. People suffer from mood symptoms such as depression as well, difficulty coping, feelings of loss and despair. Those are the most common reactions. Some people can develop other difficulties related to side effects of cancer treatments as well. And also, there are people, as I mentioned, who previously have suffered from psychiatric symptoms, where things can become much more difficult and challenging, affecting their way of thinking: problems with cognition, memory, recall, things like that. So to summarize, largely mood disturbances and mood symptoms in the forms of anxiety and depression. Panic is also a part of that, as well as post-traumatic stress. And there are others who have previous symptoms that can become more problematic. So we really try to evaluate both mood and thinking in our patient population.

Brielle Gregory Collins: Thank you so much for walking through those. And I want to talk a little bit now about exercise and how that can play a role in coping with some of these challenges. Ms. Mansfield, what is considered exercise, and what are some of the benefits of exercising during cancer?

Sami Mansfield: Great question because there are so many different terminologies around exercise and physical activity and fitness. So I think we should start there. The terminology of physical activity is probably the most broad thing that we talk about. Physical activity is anything that we do to move the body, anything from rolling over in bed, getting up, brushing your teeth, etc. Exercise is a physical activity that is more defined or maybe has a purpose. And so it might be a goal to get stronger or a goal of rehab or prehab in this particular patient population. Or some people just want to be able to walk a 5k or run a 5k. So exercise is more intentional. And that's really how we try to define it in the literature.

From a cancer patient perspective, probably the most broadly impactful side effect management tool for exercise is actually fatigue because that is where we have a depth of evidence both in physical activity and inactivity differences. And related to fatigue from the mental health side, we see a strong benefit of both exercise and physical activity in anxiety, depression, stress management, sleep quality. So I think it's important for our audience to know that anything that you do for movement is good. Having a planned and structured movement program known as exercise is going to be ideal because the bottom line is we want you to reach your goal the quickest and without kind of feeling like you're not getting a lot of benefit to movement. And so that's why exercise really does have a significant role and why I think a lot of people really strive for, "What should I do? What does that specific exercise plan look like?"

Brielle Gregory Collins: Got it. And I want to circle back to some of the challenges, Dr. Lahijani, that you outlined earlier. So how does exercise help address some of these challenges of cancer specifically?

Dr. Sheila Lahijani: Well, I love this question. And I'm very informed by what my colleague, Ms. Mansfield, just described. Exercise and physical activity, in my opinion, are so beneficial to patients who are already diagnosed with cancer, as well as those patients who may be at risk for developing cancer-- any of us, really, to reduce our risk for certain kinds of cancer. There have been many studies that have been done that have demonstrated that intentional physical activity, as my colleague termed it, in the form of exercise can ramp up certain biological processes that contribute to improvements in cognition as well as memory function. There's a factor called a "brain-derived neurotrophic factor" which can get increased with physical activity and exercise. At the very molecular level, muscle cells can play a part in reducing the progression of disease and even potentially metastases. So there's a lot to be said biologically. As well as psychologically, it really can offer quite a lot of benefit to help people manage their distress through focusing on momentary breathing, momentary muscle relaxation. And there is also a social component to it. Even if someone is participating in an activity like this by himself, herself, or themself, there is something to be said about the communal experience of being up on your feet, moving yourself, and not being so isolated and alone, which is very much a problem for patients who undergo cancer care.

Brielle Gregory Collins: That's a really good point. And Ms. Mansfield, I want to get a little bit into the specific things that people can do. So what kinds of exercise can help people with cancer cope with these challenges?

Sami Mansfield: Now, it's a great question because that's what everybody wants. What should I do, right? And I tell everybody let's just start, number 1, with avoiding as much true sedentary behavior as possible. And I say true sedentary behavior because when you are just sitting and doing perhaps mindless activities, watching TV, there's a lot of exercises that can be done when you're seated, which is great for patients that have high amounts of fatigue or balance challenges. And I tell everyone, "Lift an arm. Lift a leg. Flex your toes and feet a couple of times, roll your shoulders, and you've just moved." It doesn't have to be vigorous or difficult. It just needs to be movement. So I think just thinking about these 1-minute, we call it "exercise snacks," make a much more significant impact throughout the day than feeling like, "Oh, I've got to go to the gym and exercise for 30 minutes," or you might even have physical therapy. And the volume might be too high for people. So I want people to think first in small 1-minute movements.

But the next piece of this is, we've studied the different modalities of exercise between aerobic exercise, thinking about things like walking, or chair-based, like marching in the chair, swimming, biking, whatever that may be. And resistance training exercises that use muscles. You could do something with weights, soup cans. You could do bodyweight exercises that build muscle. We've studied them separately and together. And what we've learned is that for the emotional side effects, specifically anxiety, depression, having a combination of these movements is going to give you the most significant benefit. So my advice is do a minute of marching, whether that's in your chair or standing, then maybe do a chair sit-to-stand 10 times and a couple of countertop pushups, and you've now hit a full-body routine exercise regimen in under 5 minutes. I do think that people need to remember although there are recommendations of how much you should strive for, there's no reason you have to do the whole recommendation of 150 minutes of moderate activity per week to see benefit. Start with just 1 minute at a time, 1 movement at a time, and try to mix it up. Make it fun. Add music. Make it a challenge. Make it something that you feel that you can attain because you will feel better and also accomplished. And that does improve your well-being, to feel like, "I did that. I did my 1 thing a day." And that's really phenomenal and goes a long way to how people feel mentally.

Brielle Gregory Collins: Absolutely. And I love that term you use of "exercise snacks." I think that's a really helpful way of looking at it. So for someone who's maybe just getting started with exercise, what is your advice for them as they manage their cancer diagnosis and are trying to look toward exercise as something that they want to incorporate into their lives?

Sami Mansfield: That's definitely the question I love to answer. Because if somebody's motivated, we want to get them there quickly or get them to find a resource that helps them feel successful. I kind of go back to the whole "exercise snack" piece. I think it's more important that people realize it's better to do a little something every day than to think, "Oh my gosh, I need to hit 30 minutes today, and then for the next 3 to 5 days, I don't do anything." I really advise start small, start manageable, and look for something that you can do without having to add extra barriers to your life. As an example, if getting somewhere logistically on time doesn't work for you, start with 5 minutes of things that you can do from your home. I do think there is a really important resource within most of our cancer spaces. We have oncology rehab programs. We have trained exercise professionals that can guide you. But I think people don't realize that just moving around their house, maybe 1 flight of stairs if you can do that, is a really great way to get started. There's a lot of great YouTube videos you can try. There is definitely—talk to your physicians. They might have some great ideas. But starting daily, consistency really is going to make the biggest difference than just going, "Hey, Saturday is my day to exercise." I think we can all do a little bit in that snack fashion. And I don't know. I think we can all agree snacks are good. We all like a few snacks now and again. Definitely.

And I also kind of have this thought about-- people say, "Well, if they have cancer, should they do yoga?" And my answer is, "Well, do you like yoga?" I mean because yoga has a lot of really great resources for mental health and breath to movement and mindfulness and that grounding effect. But for someone who doesn't like yoga, which I will admit yoga is a little bit of my challenge so I push myself to do it, someone telling me to do yoga every day versus maybe exercises that I enjoy, I would be a little bit more down in the dumps about it, that you're taking away maybe what I love. So I think 1 thing, really thinking about what's the type of exercise you like to do, is it reasonable for you to continue that? If you used to run and maybe you have a lot of neuropathy in your feet, it might not be the most reasonable now. But what is the exercise that you enjoy? And that should also be part of that first thing that you do every day, not your, "Well, someone told me I should do yoga because they enjoy doing yoga," piece. And I think that's something that we need to think about in exercise. It still should be enjoyable and have good music. I think music is key as well.

Dr. Sheila Lahijani: I think it's really important to highlight as well that cancer causes so many life disruptions: disruptions to different roles, activities, functions, whatever it may be. And in speaking about intentional physical activity and exercise, it's an opportunity to create a routine and to try to lessen the impact that's caused by the disruptions.

Sami Mansfield: The pandemic certainly accelerated that for those of us who don't even have cancer. I don't know if anybody here also experienced this. But I remember I was working out in a gym setting-- and we actually had our own-- we ran a gym space at the time in Kansas City for cancer survivors. So we took that virtual. But I struggled with my routine. I was like, "Wait a minute." And I could go to my own gym that was private, right? But I really struggled with the mentality of like, "It wasn't my routine." And when your routine slips, you just feel very out of control. I think 1 recommendation we should make for all of our listeners, physicians, or those of us that are working in the field is I recommend starting every day with a minute of movement. I don't care if you're doing a few arm circles where you're waiting for your coffee or whatever, but there is something about getting your blood flow moving quickly that makes a really big difference. So whether that's, "Before I brush my teeth, I'm going to just do a couple of leg swings or a couple of countertop pushups or something simple every single day." Or if you're in bed, you do something in bed, even if it's just your foot flexion or drawing the alphabet where you're doing something to stimulate movement." You bring up a really good point, that we need to make that ritualization or routine, but make it also very accessible for people.

Brielle Gregory Collins: Absolutely. Thank you, Ms. Mansfield. That's really helpful. And Dr. Lahijani, in addition to exercise, what else can people with cancer do to cope with some of the mental and emotional impacts of their diagnosis?

Dr. Sheila Lahijani: Thanks for asking this question. And I want to also preface this by saying so much of what we're talking about is essentially what is now a field of exercise oncology, right? And so there's more and more literature available and resources that emphasize the benefits of exercise in this patient population and how the effects of other treatment modalities, such as antidepressants and psychotherapy, can be further enhanced when someone is also being physically active or having an exercise snack. So to answer your question, what I'm saying is there are many ways we can support our patients and many ways we can encourage them to have better management and control over their distress-- why there is anxiety, depression, sleep disturbances. It's really meeting people where they're at-- which Ms. Mansfield also mentioned, starting somewhere.

So when we see patients in our clinic-- and I've been known to do this, and I've done this back in the day where we would really write a lot more paper prescriptions. But even as part of my discussion points and patient instructions, I always make a point of writing, "Do some physical activity, even minimum opportunity to get yourself moving." Because what we're trying to really do is help with the circulation-- help with the circulation in the body, in the brain, really ramp up those neurotransmitters that help people feel better, remove the unhealthy oxygen, introduce the healthier oxygen. And that, in conjunction with medications, in conjunction with different psychotherapy modalities, in conjunction with progressive muscle relaxation, mindfulness, grounding techniques, can really help people feel less helpless, less stuck, less tired-- again, as I mentioned earlier, less alone, and find opportunities where they have more of a sense of control because that's part of what we're talking about here. There's a strong feeling of helplessness and lack of control when someone is diagnosed with cancer and undergoes cancer care. And this is an opportunity to help them find ways to manage their health physically, mentally, cognitively, spiritually, and feel less a sense of helplessness.

It's really encouraging me to say that there are many patients who are physically really suffering, whether it's from neuropathic pain, cancer-related fatigue, any kinds of deconditioning related to surgical interventions, other effects of chemotherapies, from depression. And it is much, much harder. And people sometimes cannot physically move. And it requires a lot more activation energy to take those steps. So part of what we do in my clinic and how we partner with our colleagues in palliative medicine as well is how can we manage people's symptoms? How can we manage their depressive symptoms, their physical symptoms? How can we help them be more cognitively stable and intact to be able to safely take those steps or to have more of that motivation or that energy or that pain relief to be able to participate in the things that we're talking about? I'm cognizant of the fact that when we have our patients and family members and caregivers listen to this, there may be some folks who are like, "But I just can't." And I have patients who tell me, "I get it, Dr. Lahijani. I understand. And I appreciate this guidance that you've offered me and the recommendations to use this medication or to consider this, but I just can't." So that problem with motivation and lack of optimal symptom management really has to be addressed in parallel, in my opinion, to really help support patients in actually participating in what we're suggesting here.

Sami Mansfield: I think that's not only an excellent point, I think you really reiterate the partnership that needs to happen with the clinicians and the exercise oncology field or oncology rehab field because the only way to really do this effectively again, and especially a more complex patient, is in conjunction with one another. And I think that we need to be mindful and remind the patients, and like you said, the family members listening, that the conversation should be had, but the clinicians really can help manage the clinical symptoms so that the exercise or rehab professionals can really get in with that, the more implementation piece, when reasonable. But I think we need to take the guilt off our patients that it's not going to be every day, even though they want to. And that's the reality, and that is okay. And some days, it is a rest day or a rest week. And that is part of the healing process of the body and a really important way to recover. And that's okay, too. I think recommendations are nice as an example. But at the end of the day, if they're not reasonable for people, we need to also take that next layer of guilt away. And they just need to be able to feel comfortable and pain-free and symptoms-managed. And that's quality of life as well.

Brielle Gregory Collins: Wow, what a great discussion. And I think the main takeaway here for anyone listening is your health care team is there to help you, and they'll work with you to figure out what's best for you, whatever that might be. So thank you so much. That was wonderful to hear both of your perspectives. And I want to talk a little bit about resources that people listening can turn to to learn a little bit more about this. So I'd like to direct this to both of you. Ms. Mansfield, we'll start with you, but where can people go to learn more about exercise and managing the mental and emotional effects of cancer?

Sami Mansfield: Absolutely. That is the key question is, what next? Really, Cancer.Net is a wonderful and evolving resource and is continuing to progress its information. So no matter when you're listening to this podcast, check out Cancer.Net. I know that the information is online. There's a ton of resources right there. There are some other really great programs and resources. I would talk to your clinicians about things like cancer-specific rehab programs that you may have access to, which many have insurance coverage. And I tell people you don't have to feel broken to get cancer rehab. There are a lot of ways that cancer rehab can help you even just manage general fatigue or cognition. Referral to a speech-language pathologist can be helpful with some of those techniques about memory and chemobrain. So those are resources. In addition, there are qualified exercise professionals through the American College of Sports Medicine that have training and certifications and have experience. That can be another resource that can help you. I would also advise people to think, "You don't always have to have a cancer professional." There are great fitness professionals that may fit-- yoga professionals or other types of exercise modalities. So don't always feel like you have to find the "cancer person." But depending on your symptoms or side effects, having a professional that understands what it means when you say neuropathy can be very helpful. So I would definitely start with those resources first and then branch out as you feel comfortable.

Dr. Sheila Lahijani: She responded to that question beautifully. And to add to what she just shared, looking at what your own cancer center, your place of health care where you receive it, what's available. There are many websites through the different cancer centers and medical centers that have wonderful patient-facing and family-facing educational resources. The American Cancer Society also has a lot of helpful information. As Ms. Mansfield mentioned, Cancer.Net is a wonderful resource. And also to emphasize that there are programs that can be done virtually, especially in this era of this pandemic. While we encourage in-person interactions, however it's safe and feasible because there's so much benefit to feeling less alone and isolated and maybe having that direct 1-on-1 attention, we recognize that many patients because of their immune compromise or because of whatever challenges they may have with respect to support or transportation or finances, whatever it may be, it might be harder to access care or services where someone lives. And so there are programs and services that are available online. And that shouldn't be limiting. That should be something to really think about and consider.

Actually, I was in a meeting recently where I learned about an organization called the Maple Tree Cancer Alliance, which has programs available through different cancer centers as well, among which is my center, Stanford. And so there are plenty of resources available. And with that, I will also say pick something. Choose something. You don't need to look at everything and try to do everything. Take a look at what's available to you, what's accessible to you, what makes sense, and just try it out, and see if it helps. And if it doesn't help or if it's not providing you any kind of immediate benefit, look to see what other options there are. We have so many patients tell us that they're trying to follow through on our recommendations, and people want to be, quote-unquote, "good patients." And that can get very overwhelming. People in large part want to feel better. They want to get better. That doesn't mean you have to take advantage of every single resource or recommendation that's being offered to you. Take a look at what's close to you, what you can access, and how you can make it work, and start somewhere.

Brielle Gregory Collins: Absolutely.

Sami Mansfield: And on that start somewhere, the other thing to really think about too - and Dr. Lahijani really said this - is you don't have to do-- everything at once can be so overwhelming. This is the long game. And so this exercise piece should be a lifestyle behavioral change piece that works for you in the long-term. It isn't about just, "Here I am. I want to get through just this 1 specific piece in my life." Look for something that you enjoy because you're going to be much more likely to continue. And then thinking about that support circle, it may be someone that has a similar diagnosis or understands what you're going through or have gone through. And it may be somebody that you have met or a family member that has never experienced this but is that person that you can vent to or is your accountability partner or your meet-for-a-walk or a virtual walk partner. I think we need to be really mindful, be creative about this. It should be enjoyable. It should be something that fits you. And at the end of the day, there's no right way to exercise. I think we'd all do something different here today if we all could choose. And that's okay too. Cancer is very individual, and so is this piece of that. So I think that's really empowering for all of our listeners to remember.

Brielle Gregory Collins: Definitely. And that's so nice to hear, as far as there's no right way to exercise, I think that's a really helpful way of looking at it. Well, thank you both so much for your time today and for sharing your expertise, Dr. Lahijani and Ms. Mansfield. It was so great having you both.

Sami Mansfield: Thank you so much for having us.

ASCO: Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

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ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In the Research Round Up series, ASCO experts and members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's episode, our guests will discuss new research in multiple myeloma, breast cancer, and cancer in adults 60 and over that was presented at the 2022 ASCO Annual Meeting, held June 3-7.

First, Dr. Sagar Lonial discusses a study on treatment for newly-diagnosed multiple myeloma in people under 65.

Dr. Lonial is a professor of Hematology and Medical Oncology at Winship Cancer Institute at Emory University, where he also serves as Department Chair. He is also the Cancer.Net Associate Editor for Myeloma.

View Dr. Lonial's disclosures at Cancer.Net.

Dr. Lonial: Hello, I'm Dr. Sagar Lonial from the Winship Cancer Institute of Emory University in Atlanta, Georgia. And today I'm going to discuss one of the Plenary abstracts at ASCO 2022, which was the DETERMINATION study, again, presented at the ASCO Annual Meeting. For the sake of disclosure, I just want to make sure I list that I was an investigator on this study. I also have consulting relationships with Takeda, Celgene, BMS, Janssen, and other companies that have agents in the context of multiple myeloma.

So the reason I want to talk about this study today is I think it's a really important study that was designed over a decade ago to really ask the question, with a really powerful induction regimen that uses what we now call the RVd regimen, lenalidomide with bortezomib and dexamethasone, do you really still need to have high-dose therapy and autologous transplant as part of the treatment approach?

And so the trial was a very simple randomized trial that everybody received RVd induction. And then there was a randomization between early transplant and then going on to consolidation and continuous lenalidomide maintenance versus no transplant going on to consolidation and lenalidomide maintenance. So both arms actually received continuous lenalidomide maintenance, which is really one of the important endpoints of this study overall. And the reason I say that is there was a smaller study done in France a few years previous to this where patients only received 1 to 2 years of lenalidomide maintenance. And in that trial, clearly the use of transplant was better. And the remission duration for the group that received the transplant was about 48 months. So the question was, with continuous lenalidomide maintenance, can you make that longer?

So randomized trial, over 600 patients were randomized between these 2 arms. And the follow-up now is somewhere around 7 years in total. And what was demonstrated both in the ASCO Annual Meeting as well as in the paper that came out at the same time in the New England Journal of Medicine was that the remission duration was clearly longer in the group that had the transplant than the group that did not, even with both arms receiving continuous lenalidomide maintenance. And it was almost 66 months in the group that received the transplant, 21 months longer, almost 2 years longer than the group that did not receive the transplant. And so I think this is really important because what it says is that even in an era of really good induction therapy, transplant continues to offer significant benefit in terms of progression-free survival.

Now, the reason progression-free survival is so important in this study is that we know that no time is more sensitive for treatment of myeloma than that first time we treat the patient. And so prolonging that first remission is really important because the disease is at its most sensitive at that time point. Now, there were questions about overall survival. Should we see an overall survival benefit? And I'll tell you, A, this trial was never designed to measure an overall survival benefit. And, B, the median survival for myeloma patients is now between 10 and 15 years on average. And so with only 7 year follow-up, it seems to me unrealistic to expect this to have a survival benefit at this early time point. So rather than saying there's no difference in overall survival, I think it's a fair statement to say at the short follow-up we have, there is no difference in survival. But I actually don't think survival is the right endpoint for newly diagnosed myeloma trials in fit patients because we do have so many important treatments to discuss.

Now, there was also discussion about adverse events. Obviously, the quality of life during the transplant dropped a little bit. Not a big surprise. That lasted about 2 to 3 weeks, and then quickly, by 3 months out, returned back to baseline for almost every patient in the study. Additionally, there was a concern about second primary malignancies. If you look at this data, it's really no different than what we saw in the French study. There was a slightly higher risk of second primary malignancy, but we know that this is the case not only in myeloma, but in patients who receive alkylate-based therapy. And despite that, the progression-free survival was 2 years longer in the group that received the transplant than the group that did not.

So I think, in summary, this is really an important trial because there are many groups that are making the case that perhaps we don't need transplant in this modern era of myeloma therapy. And I think that it's important to recognize that what we're looking at are not short-term endpoints. We're not looking at early MRD (minimal residual disease) negativity. What we're looking at is really ultimate measurement of clinical benefit, which to me is prolonging that first remission as long as you can. And so this trial clearly demonstrates that for young, fit patients, transplant continues to offer significant benefit, almost 2 years of benefit with continuous lenalidomide maintenance. And while there's a push to say perhaps we can think about which patients may or may not need a transplant, honestly, as clinicians, we're not good enough to make that prediction. And what I think is really important is that we not lose sight of trying to prolong that first remission with the best tools that we have. And I think even in this modern era of 2022, high-dose therapy and autologous transplant continues to be one of those tools, and we want to use it to maximize the duration of that first remission. So thank you again for listening to this brief summary of the DETERMINATION trial presented at the 2022 ASCO Annual Meeting and published in the New England Journal of Medicine.

ASCO: Next, Dr. Norah Lynn Henry discusses new treatment advances for people with metastatic breast cancer, as well as 2 studies in early-stage breast cancer.

Dr. Henry is an Associate Professor in the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and is the Breast Oncology Disease Lead at the Rogel Cancer Center. She is also the Cancer.Net Associate Editor for Breast Cancer.

View Dr. Henry's disclosures at Cancer.Net.

Dr. Henry: Hi. I'm Dr. Lynn Henry, a breast cancer oncologist from the University of Michigan Rogel Cancer Center. Welcome to this quick summary of updates in breast cancer from the 2022 ASCO Annual Meeting. I have no conflicts of interest for any of the trials that I will talk about. First, I'm going to give a very brief overview of the types of breast cancer, then talk about some research that was presented on both metastatic and early-stage breast cancer. As a reminder, there are multiple kinds of breast cancer. Some breast cancers are called hormone receptor-positive or estrogen receptor-positive and are stimulated to grow by the hormone estrogen. We typically treat those cancers first with antiestrogen treatments, which block estrogen or lower estrogen levels. Other breast cancers are called "HER2 positive." These are often more aggressive cancers, but because they have extra copies of HER2, they often respond to treatments that block HER2. Finally, there are breast cancers that don't have hormone receptors or very much HER2. These are called triple-negative breast cancer and are also often aggressive cancers.

One of the biggest stories from the ASCO Annual Meeting was the results of the DESTINY-Breast04 trial. In this trial, researchers studied a type of medication called trastuzumab deruxtecan, which is also called Enhertu. This drug is a combination of the anti-HER2 antibody, trastuzumab, plus a chemotherapy drug, and the antibody targets the drug to the cancer sort of like a guided missile. Trastuzumab deruxtecan is currently routinely used to treat patients with metastatic HER2-positive breast cancer. Now, the interesting thing is there was already data from studies that suggested that this drug might also work against breast cancers that have some HER2 receptors on the surface of their cells, but not so many that they meet the true definition of being HER2 positive.

For the DESTINY-04 study, patients' tumors had to have either 1+ or 2+ HER2, which some people called "HER2 low," and could be either estrogen receptor positive or negative. Two thirds of the patients were treated with trastuzumab deruxtecan, and the other one-third were treated with 1 of 4 different standard chemo regimens that their physician thought was the best treatment option for them. Treatment with trastuzumab deruxtecan was shown to lengthen the time people were able to remain on treatment. Importantly, it was also shown to increase the overall survival of patients compared to standard chemotherapy by more than 6 months for patients with estrogen receptor-positive cancer and by more than 10 months for patients with estrogen receptor-negative cancer. Since this is a drug that we currently use to treat patients with other types of cancer, we actually know a lot about its side effects. One key toxicity is it can cause a very severe inflammation of the lungs in a very small subset of patients. So this is something that we have to watch for very carefully. Otherwise, it is a relatively well-tolerated drug, especially compared to standard chemotherapy. The main side effects are nausea and fatigue. Another clinical trial presented at ASCO called TROPiCS-02 also studied a drug that is currently used to treat a different type of breast cancer. In this case, the drug is sacituzumab govitecan, also called Trodelvy. It is also a combination of an antibody that is targeted against cancer cells plus a chemotherapy drug. Sacituzumab govitecan is currently approved to treat metastatic triple-negative breast cancer.

In the TROPiCS-02 trial, however, it was tested to see how effective it is for treating hormone receptor-positive, HER2-negative metastatic breast cancer. All of the patients enrolled in this trial had already been treated with antihormone therapy medications as well as at least 2 chemotherapy regimens. Half of the patients were randomized to treatment with sacituzumab govitecan, and the other half were treated with 1 of 4 standard chemotherapy drugs that their physician thought was the best for them. Those patients who were treated with sacituzumab govitecan had a longer time on average that the treatment worked compared to those who received standard chemo. They also had improved quality of life based on responses that the participants themselves provided on questionnaires. Although the overall benefit was rather modest, this drug may represent a new treatment option for patients with hormone receptor-positive, HER2-negative metastatic breast cancer, although at this time it isn't yet approved for treatment of this type of breast cancer. Both of these are examples of being able to take drugs that have been shown to treat 1 type of cancer and potentially expand it so that they can be used to benefit more patients with breast cancer. These drugs are also being tested to see if they are beneficial for treating early-stage breast cancer. So we await more hopefully very exciting results in the future. To switch gears a little bit, I'll now talk about another study I found interesting. This one is in the setting of early-stage breast cancer. So typically, radiation therapy is recommended after lumpectomy since it reduces the likelihood of cancer returning in the breast. However, questions have arisen about how much benefit radiation is actually providing for some patients whose risk of having cancer return in the breast is really low to start with. Therefore, these patients may be at risk of the side effects of radiation as well as other risks, such as financial problems, without actually getting much benefit from the treatment.

Therefore, this trial, called LUMINA, evaluated whether radiation therapy was beneficial after lumpectomy for patients who have small, low-risk breast cancers and no lymph node involvement. The trial included 500 women who were at least 55 years of age with invasive ductal cancers that were no more than 2 centimeters in size. They had to be estrogen receptor-positive, HER2-negative, either grade 1 or 2, and Ki-67 low. Everyone had to be planning to take antihormone therapy for at least 5 years. During the 5-year follow-up period, a total of 10 patients out of 500, about 2.3% of all patients, had their cancer return in the breast. The researchers therefore concluded that for patients with this type of very low-risk breast cancer, it is reasonable to omit radiation therapy and just take endocrine therapy. Similar results have previously been shown for patients over the age of 70 with small lymph node-negative low-risk cancers, but this trial expands that option to patients who are as young as 55. Finally, I will touch briefly on the updated results from the ABCSG-18 clinical trial. So this trial enrolled postmenopausal women with early-stage estrogen receptor-positive breast cancer who are being treated with aromatase inhibitor therapy. Aromatase inhibitors are known to cause reductions in bone density. This trial therefore evaluated a medication called denosumab, also called Prolia, which is used to treat osteoporosis. Participants were randomized to treatment every 6 months with either denosumab or a placebo. They found that the patients who were treated with denosumab were half as likely to have a bone fracture. Importantly, patients treated with denosumab also had an improvement in bone density despite taking the aromatase inhibitor medicine, whereas those who received placebo had a decrease in their bone density over time.

The other very interesting thing from this study is that patients who received treatment with denosumab were less likely to have their breast cancer return or to develop a new cancer during the 8-year follow-up period. So it's actually already recommended that postmenopausal patients with all types of early-stage breast cancer consider treatment with a different type of bone strengthening medicine called a bisphosphonate as part of their breast cancer treatment. The goal is to further reduce their risk of cancer returning. These new results will now lead experts to debate whether to also include denosumab as a potential additional breast cancer treatment option, not just to help protect people's bone density.

There were a lot of other research findings presented that were related to treatment for both early-stage and metastatic breast cancer at the meeting. Importantly, we got glimpses of the many new drugs on the horizon for treatment of breast cancer, and we eagerly await the results of large, randomized trials so that the drugs that work can be used to care for patients with breast cancer. But for now, that's it for this quick summary of important research from the 2022 ASCO Annual Meeting. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you.

ASCO: Thank you, Dr. Henry.

Finally, Dr. Shakira Grant discusses 3 studies that looked at cancer in people 60 or older. This field is also known as geriatric oncology.

Dr. Grant is an Assistant Professor in the Divisions of Hematology and Geriatric Medicine at the University of North Carolina at Chapel Hill and a board-certified Geriatric Hematologist/Oncologist.

View Dr. Grant's disclosures at Cancer.Net.

Dr. Grant: Hi, everyone. I am Dr. Shakira Grant. And I'm an assistant professor at the University of North Carolina at Chapel Hill. I'm also a clinician scientist with a focus on social disparities and how they influence the health and aging of older adults with cancer, primarily multiple myeloma. And for today's talk, I have no relevant conflicts of interest to disclose.

It's such a pleasure to be able to talk today about the ASCO 2022 geriatric oncology and presenting key studies, which I believe were really practice-changing or really set up the foundation for informing future research directions. And to start us off, I wanted to start us with abstract 12012 by Dr. Mackenzie Fowler. And this was presented based on the University of Alabama at Birmingham's actual research group. And the title of their presentation was "Rural-Urban Disparities in Geriatric Assessment Impairments and Mortality Among Older Adults with Cancer." And this was the result of a large registry study, predominantly patients with gastrointestinal cancer-- so cancers such as liver cancer, colon cancer. And what the authors really wanted to do here was to explore if whether or not living in a rural location, for example, is associated with having an impairment based on what people report in their ability to function at home, their quality of life. And they also wanted to see whether or not where you live, meaning a rural location, whether that can be associated with how long you are expected to live or your overall survival.

So this was really a study that took patients who were truly older. There were patients who were above the age of 60. As I mentioned, these were patients predominantly with cancers of the liver, the colon, and the pancreas. And patients completed a baseline, what we call a geriatric assessment, to try to assess their overall or global health. And on these assessments, patients are asked questions about how they would rate their physical function and their quality of life. And what the authors found here is that in general, when patients lived in rural areas, this was associated with patients self-reporting more functional deficits, meaning that they reported that they had impairments in the ability to function at home from a physical perspective. They also had impairments in quality of life—so how you rate your general life and how you're doing from a day-to-day basis. And this was impaired if you lived in a rural residence. And then, importantly, this study also showed that living in a rural location—and, again, this study was centered in Alabama—that that was also associated with a reduced overall survival, meaning that people were found in rural areas to live a shorter life with these cancers compared to those who live in non-rural places or, as we call it, urban.

And I think why I chose this particular study is because it's one of the first studies using a large data set of almost 1,000 patients that they have enrolled and really looking at the idea of the physical environment, so where a person lives, and how that really interacts with everything else to influence the health of an individual. And this study, I believe, really lays the foundation for an area of work in geriatric oncology where we are moving away from just thinking about the older adult, but we're also thinking about the older adult and the other identities. So we're really considering the sociocultural influence. So we think about race. We think about socioeconomic status, income. But now, we're also including the physical environment. And that is where people are living and spending the majority of their time. And that is in this study classified as rural-urban residency. So for this study, overall, I would say that this is really moving the field forward in a direction where we're moving away from just looking at just older adults, but we're thinking about older adults and all of the other stressors that they face, especially when they live in the community and how that impacts their health.

The next study that I wanted to highlight was a study that was performed by Dr. Heidi Klepin at Atrium Health, Wake Forest Baptist. And this was a study that looked at evaluating the association between an electronic health record-embedded frailty measure and survival among patients with cancer. Again, this was an older adult population. It was just over 500 patients involved, and patients were over the age of 65. They had a new diagnosis of the most common cancers, which are lung cancer, colon cancer, and breast cancer. And the good thing about this particular study is that it sought to use data that is readily captured in the electronic health record to characterize a patient as fit, prefrail, and frail. So why is that important for the geriatric oncology community and even beyond is when we're dealing with older adults, we're always thinking about ways in which we can actually characterize their fitness and their ability to hence tolerate their therapies, being chemotherapy, and how likely they are to die if they're having these functional impairments.

And so importantly, what this study showed was that in their sample, they found that up to 17% of people were characterized as frail using this index. And the significance of this finding is that when they looked at how long people were likely to live with these cancers, breaking it down according to if you were fit, prefrail, or frail, those who were frail had the shortest overall survival. So it means the time from which they were diagnosed until they die was much shorter than any of the other categories. And that equated to a difference between those who were fit and those who were prefrail of 10 months for those who were frail for overall survival and more than 54 months for those who were actually considered to be fit. So this is really, really important because what we are seeing is that if you are really fit, you are living on average with these cancers—the overall survival, at least for their institution, was more than 54 months. But then as you move across that spectrum of fitness, we're actually seeing that your survival decreases significantly.

And so why is this important? So this is important because it's one of the first studies that is actually looking to operationalize the frailty measure for us to be able to potentially use and adapt into other health systems using data that we already collect. So it's no longer burdensome on patients to try to fill out additional forms or for other staff to be involved and collect this data. And this data is showing us that there is an association with this particular frailty index and the ability to predict overall survival-- so, again, a critical study in the geriatric oncology population looking at patients with the 3 most common types of cancer, which are lung cancer, colon cancer, and breast cancer, and really showing us that there is a way potentially to operationalize how we characterize the fitness level of an older adult and then using that data not just to say, "Yes, this person is frail," but for us in real-time to see results where we can see that there is a significant difference in terms of overall survival.

Importantly, this is going to be a study where we continue to watch closely the developments over the next few years, especially as the authors and the research team note that their next steps involve looking at how to study how these frailty measures, or the frailty scores that people get when they come in and they're at baseline, how this changes throughout the course of treatment. And that has a lot of implications because now, we have the potential to start thinking about using a frailty-adapted approach to caring for older adults with cancer. What that means is when you're getting your treatment and we are following these scores, as we see things changing, this may be an indicator to us that, "Hey, we need to make some modifications in response to these frailty measures to make sure that our older adult population is able to tolerate their chemotherapies and have maximum benefit while also enjoying a good quality of life."

So finally, I want to highlight this third study. And this was a study that was presented by Dr. Etienne Brain. And. Dr. Etienne Brain was also this year's B.J. Kennedy Award recipient. And each year ASCO recognizes the B.J. Kennedy Award recipient as an outstanding investigator who has made significant contributions in the area of research and clinical care of older adults with cancer. In this particular study, Dr. Etienne presented on behalf of his team the final results from a study that was looking at using endocrine therapy with or without chemotherapy for older adult women, so characterized as those who were over the age of 70, with a diagnosis of estrogen receptor-positive, HER2-negative breast cancer. And the importance for this study is that the question they sought to examine was whether or not patients who are in this age range still derive a benefit from receiving chemotherapy in addition to endocrine therapy.

And what this study really showed is that there was no survival difference. Meaning when they looked at the data for 4 years, those who got chemotherapy plus endocrine therapy lived just as long as those who also just got endocrine therapy alone. And why this is important is because when you think about giving chemotherapy to an older adult population, as oncologists, we are always weighing the risks and the benefits associated with treatment. So we're always thinking about how tolerable is this drug likely to be? We want to minimize side effects because, at the end of the day, our goal is to treat the cancer, but we also want to focus in on the outcomes that matter most to the older adult population. And in general, these are things like maintaining your mobility, maintaining your mentation, maintaining good quality of life. And so we really want to make sure that we're balancing those risks. And this is why this particular study showing that with chemotherapy or without chemotherapy added to endocrine therapy, there seems to be no survival difference. This could be a way in which we move the field forward in thinking about a select group of patients with breast cancer and whether or not those patients truly need that extra toxicity or burden associated with using chemotherapy or whether endocrine therapy is enough.

So with that, I will say across these 3 studies, even though they study different things-- we saw 1 study that looked at the intersectionality between older adults in terms of their chronological age but now starting to examine the influence of physical or social context and how that influences the health and outcomes for individuals with primarily gastrointestinal cancer. We also looked at the development of an electronic frailty index in patients with 3 most common solid tumors - lung cancer, colon, and breast cancer - and found that by using this frailty index collecting readily available data, that there was an association with predicting overall survival. And we saw that those who were characterized as frail had one of the shortest overall survivals. And then finally, in this study, looking at endocrine therapy alone versus chemotherapy and endocrine therapy, we saw that there was no survival difference again in an older adult population. And so what we are seeing here is a theme emerging as the importance of comprehensive evaluations of older adults and the importance also of these measures, when integrated across the research continuum, that they are useful in terms of predictive prognostic abilities and really lay the foundation for future research. So with that, I want to thank you for your time and thank you for listening.

ASCO: Thank you, Dr. Grant.

You can find more research from recent scientific meetings at www.cancer.net.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

The beginning of the COVID-19 pandemic brought with it confusion, fear, and uncertainty for most people around the globe. These feelings were often heightened for people with cancer as they experienced disruptions or changes in care, such as following greater safety precautions at their treatment centers, having their appointments shifted to televisits, and facing delays in recommended cancer screenings.

As a response to the COVID-19 pandemic, Cancer.Net developed several resources for people with cancer, including its post "Coronavirus and COVID-19: What People With Cancer Need to Know," written by Dr. Merry Jennifer Markham. After publishing this post on March 3, 2020, Dr. Markham reviewed and updated the post for 650 days straight to make sure people with cancer were receiving the most up-to-date and relevant information about COVID-19. The post went on to receive the Award of Distinction from the eHealthcare Awards in the Best COVID-19 Pandemic Related Communications category and was translated into Spanish, Portuguese, Russian, and Arabic.

In this podcast, ASCO's Chief Medical Officer, Dr. Julie Gralow talks with Dr. Markham about her role in creating information for people with cancer throughout the pandemic, how the pandemic has shifted her perspective, and where she sees the future of the pandemic response headed.

Dr. Gralow: Hello. I'm Dr. Julie Gralow, ASCO's Chief Medical Officer. Today, I'm talking with Dr. Merry Jennifer Markham, an ASCO volunteer and the Cancer.Net Associate Editor for Gynecologic Cancers. Cancer.Net is the patient information website of ASCO. Dr. Markham is also chief of the University of Florida, Division of Hematology and Oncology, a clinical professor in the University of Florida College of Medicine, and the associate director for medical affairs at the University of Florida Health Cancer Center.

Dr. Markham played a key role in ensuring that ASCO provides up-to-date information about COVID-19 for patients, survivors, and caregivers through Cancer.Net. Since March 2020, she devoted a remarkable amount of time and energy to this endeavor, including a stretch of 650 straight days of reviewing and updating our patient information about coronavirus. Wow. That's true dedication, Merry Jennifer. So I would like to kick it off to you, Merry Jennifer. First of all, thank you so much for everything you've done during these past couple of years in keeping our Cancer.Net website up to date for patients during these incredibly challenging times. I'm looking forward to having a conversation with you about all of this.

Dr. Markham: Thank you so much. It's been an honor and a pleasure. And the Cancer.Net team has been just fantastic to work with.

Dr. Gralow: Great. Glad to hear it. So Merry Jennifer, when you suggested that ASCO provide some patient-focused content on COVID and cancer, did you think we'd still be talking about this 2 years later?

Dr. Markham: Oh, I had no idea what to expect. No. I think I, like many of us, thought that this would be a very time-limited event and maybe by the Christmas time of 2020, that we would be done. We were all, of course, disappointed to learn that that was not how a pandemic plays out, but I definitely had no idea what my one email to the group would lead to.

Dr. Gralow: What do you remember about March of 2020?

Dr. Markham: It was a really scary time and a very uncertain time. None of us really knew what was going to come. We were watching how the pandemic or just the viral infection was playing out at the time in other countries, but really, we're not sure what was going to happen to our patients. And I was coming off a stint, I believe - the timing is a bit of a blur - on the communications committee for ASCO. And communications is something that I am passionate about, cancer communication with patients and with other colleagues. And I recall being in clinic and answering questions from patients. And really, it felt like there needed to be some broader level of communication that our patients could refer to you but also colleagues and people around the world. That's what I remember. And I remember reaching out and saying, "Hey, I wonder if maybe ASCO should do something." I didn't intend to volunteer myself to do something, but somebody needed to jump in, and I was ready.

Dr. Gralow: Well, I was still practicing at the time, and I know all the different questions that we were getting. It was such a confusing time. We didn't have information. It was changing on a daily basis. I'm impressed that you thought that we were going to be dealing with this maybe even until the end of 2020 because I was thinking, "Oh, 3 or 4 weeks. We can all quarantine for 3 or 4 weeks. Right?" And here we are more than 2 years later. So you worked on the content for 650 days straight. I mean, every single day for 650 days, you looked to make sure that what we had on there was accurate, and now we backed off a little. But you're still looking at the content a couple of times a week. How has that level of focus on COVID-19 affected your perception and experience of the pandemic?

Dr. Markham In the very beginning, the content was really updated daily. I think something was changing on a daily basis. And so it became part of my morning habit, first thing in the morning with a cup of coffee if I had time for that, to read whatever was happening in the news that day and just paying attention to where we were headed, knowing that there would be changes. In the beginning, there was not enough masks, so we weren't recommending everyone "Go out and buy surgical masks." And then the policies changed on that as we had plenty of masks and then, of course, vaccines and so on and so forth.

I think I felt, like many people, a loss of control when the pandemic happened. Right? I think that so many people felt the sense of loss and the sense of uncertainty. And it reminded me actually of what patients with cancer probably experience with a new diagnosis, the sense of loss and uncertainty for what the future holds. And I think like many of my patients who really want to dive in deep to the research of their own cancer and treatment course, it actually gave me a sense of comfort to delve deep into the facts of what we were learning on a daily basis about COVID. Having that knowledge at my fingertips and being able to put it into layman's terms really did help me, I think, not become emotionally tied up in all of the sadness of the pandemic and the loss of travel and the loss of being able to be with loved ones. So for me, it was a little bit of a coping mechanism, I think. I didn't realize that at the time, but in hindsight, I really think it was.

Dr. Gralow: So becoming a true expert in COVID and cancer was your coping mechanism. That's interesting because you were the leading authority here on what everyone was recommending. Do you have any particular moments, good or bad, that really stand out for you from those early days?

Dr. Markham: I think what stands out the most is we focus so much on science as practitioners of oncology and in these health professions and as scientists. And I remember being very disappointed and hurt whenever I encountered someone, whether it was a patient or a family member or a colleague or-- not colleague but acquaintance, perhaps, who didn't believe that this was a real thing. And I was really pouring my heart and soul into the work of providing patient education on this and trying to do the same in my own clinic and with my own family members. And to have people brush it off as a non-thing, it was hurtful, and it was also just very disappointing as a physician and scientist.

Dr. Gralow: And things were changing fast. Now, you yourself ended up with a COVID diagnosis at the end of 2021. Did that personal experience change the way you viewed ASCO's roles in supporting people with cancer throughout the pandemic?

Dr. Markham: So I was minimally symptomatic, which was really thanks to science and thanks to the vaccines and having boosters. So number 1, it was very mild. But like many people who have a diagnosis that's new to them, I was nervous. And so I did feel reassured, though, because I had a pretty good understanding of what was happening and what was going to happen, and I knew that I was protected because of the vaccine and boosters. But it can be a scary time, and I think that it just gave me a little more insight into what people who I've taken care of, who have cancer and then have experienced a COVID diagnosis, have felt. Unlike my patients with cancer, I'm not immunocompromised, so I felt pretty comfortable. But it can certainly be scary. And I did have that appreciation for-- not just the infection but having to isolate myself from my family, I think that really was the hardest part and the inconvenience of it.

Dr. Gralow: Well, I'm glad you just had a mild case, and hopefully, you have no residual symptoms. But it is interesting when you have, either within your family or yourself, a personal confrontation, either with COVID or with cancer, that it gives you a different perspective.

Dr. Markham: Absolutely. That is so true.

Dr. Gralow: So we're now 2-plus years into the pandemic. I know you don't have a crystal ball, and I know we've thought we were on the downswing and things picked up again. But where do you see this going? I mean, not just COVID itself but public health, immunizations, the whole pandemic awareness. Where do you see this going in the U.S. and worldwide? We've had the flu coming around every season. We didn't wear masks. We have vaccines. Not everybody got vaccines. What are we going to learn from all of this, and where do you see the future will be?

Dr. Markham: I think that one of the major learning experiences that all of us who are in medicine and health care and those in health communication and health policy-- what we have learned is that science communication really does matter, and it's hard to do it in a very rapid-fire pace and do it well. But I think we've all seen examples of how communication around factual data and removing misinformation is actually critical. I would love to see this pandemic go away, but I think that what we've seen over the last couple of years with the new variants coming out, it's clear that we're not going to have 99% of our population vaccinated. I think, really, on all fronts, vaccination uptake is not that high. So there will be people who are either unable or unwilling or who will defer getting vaccinated. And unfortunately, this will lead to these waves of new variants coming like the current variant that is circulating. But I do think that there is hope.

One of the reasons that a lot of my patients delayed getting vaccines in the beginning-- many of mine did, but there were some holdouts who really were not comfortable getting vaccinated. There is now more time. And so we do have more safety data, and we know that the vaccinations are safe against-- the COVID vaccinations are safe. So I think that I have seen more patients in those last 6 months become vaccinated. They were holdouts initially, and now more are doing it. And I'm hopeful that this trend will continue. I do think there are pockets where we are seeing vaccination rates start to pick up again. I don't know. I'm happy to keep reviewing content, though, and updating. The updates have become a little less frequent, which is great. I love when our focus on updating is really on new therapies and new vaccines and new vaccine sequences and schedules. So I think we're in a fairly stable place - knock on wood - right now.

Dr. Gralow: In our immunocompromised population, which is only a subset of all of our patients with cancer, do you think we'll see more mask wearing in the future?

Dr. Markham: I do. I do think that actually this is one area where we, as a culture, have probably begun to shift in the United States and especially among people who have a personal risk or a family member with a risk factor that might increase their chances of severe COVID. Just a personal anecdote. I traveled internationally for the first time since COVID a couple of weeks ago, and my entire family, all vaccinated and boosted, wore our masks, as it's the federal requirement to do so on planes. However, we landed in an international location where that was not a requirement. None of us wanted to take our masks off. We felt more comfortable, and I saw a lot of people who also remained masked even though it was not a requirement. So I do think there's a shift in this culture. I'm as tired of the masks as anyone, but it really does have a protective measure and is, I think, important, especially for our patients who have a weakened immune system or other medical risk factors for developing COVID or other infectious diseases.

Dr. Gralow: So kind of in closing, you did such tremendous work for ASCO, for our patients with these regular updates. But what's the experience meant to you as an ASCO member and a member of the oncology community?

Dr. Markham: I joined ASCO when I was a fellow, and I was taught the importance of our organization by my faculty members and my mentors. And as soon as I realized I could, I volunteered to serve on ASCO committees and task forces. And it has been one of the most rewarding parts of my career. And it's something that I encourage junior faculty and fellows to do as well. ASCO is such a leading voice. It is the leading voice for oncology care globally. And just the opportunity to contribute something back has really meant the world to me. It's been an honor to be able to do this work.

Dr. Gralow: Well, on behalf of ASCO, I want to thank you again for all of your commitment to this. We're thrilled to have you as a volunteer, and we will continue to call on you as a volunteer. Really appreciate that. And I do know that throughout the COVID-19 pandemic, a lot of what ASCO was posting, a lot of the webinars we had, etc., were being used around the world. And you contributed majorly to that as well. So for that, I thank you. And I thank all of our listeners. This has been Julie Gralow and Merry Jennifer Markham talking about our Cancer.Net COVID-19 information that Merry Jennifer tirelessly led daily, essentially, for a couple of years. So thank you so much for that. It's been great talking to you.

Dr. Markham: Thank you.

ASCO: Thank you, Dr. Gralow and Dr. Markham. Find all of Cancer.Net's resources on COVID-19 and cancer at www.cancer.net/covid19.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's episode, 4 Cancer.Net Specialty Editors discuss new research in prostate, bladder, kidney, and testicular cancers presented at the 2022 Genitourinary Cancers Symposium and 2022 ASCO Annual Meeting.

This episode has been adapted from the recording of a live Cancer.Net webinar held June 15th, 2022, led by Dr. Neeraj Agarwal, Dr. Timothy Gilligan, Dr. Petros Grivas, and Dr. Tian Zhang.

Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah.

Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig (TOSS-ig) Cancer Center.

Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine. He is also an associate member of the clinical research division at the Fred Hutchinson Cancer Research Center.

Dr. Zhang is an Associate Professor of Internal Medicine at UT Southwestern Medical Center and a medical oncologist at the Harold C. Simmons Comprehensive Cancer Center.

Full disclosures for Dr. Agarwal, Dr. Gilligan, Dr. Grivas, and Dr. Zhang are available at Cancer.Net.

Greg Guthrie: Good afternoon, everyone. I'm Greg Guthrie, and I'm a member of the Cancer.Net content team. I'll be your host for today's Research Round Up webinar focusing on cancers of the genitourinary tract. Cancer.Net is the patient information website of the American Society of Clinical Oncology, known as ASCO. So today, we'll be addressing research from 2 2022 scientific meetings, the ASCO Annual Meeting held in Chicago in June and the Genitourinary Cancers Symposium held in San Francisco in February. Our participants today are all Specialty Editors of the Cancer.Net Editorial Board, and they are Dr. Neeraj Agarwal of the Huntsman Cancer Institute in University of Utah, Dr. Timothy Gilligan of the Cleveland Clinic Taussig Cancer Center, Dr. Petros Grivas of the Fred Hutchinson Cancer Research Center and University of Washington, and Dr. Tian Zhang of the University of Texas Southwestern Medical Center. Thank you, everyone, for joining us today. So starting us off today is Dr. Agarwal who will be talking about research in prostate cancer. Go ahead, Dr. Agarwal.

Dr. Agarwal: Hi. Thank you, Greg. So I'd like to start with 2 studies. They both are in prostate cancer which will be followed by my colleagues presenting studies in other cancers in bladder cancer and kidney cancer. So I'll start with this abstract, which was highly discussed by the doctors at the ASCO Annual Meeting a few weeks ago, and it has a lot of relevance in our practice. So this is abstract #5000 presented by Dr. Michael Hofman, and this was the update on a clinical trial which compared lutetium PSMA-617, or lutetium PSMA, to put it simply, with cabazitaxel in patients with metastatic castration-resistant prostate cancer who had disease progression after receiving docetaxel chemotherapy.

So, who were the patients who were enrolled on the study? These patients had, as I said, metastatic castration-resistant prostate cancer, who had disease progression after docetaxel chemotherapy, and who had to have high PSMA-expressing prostate cancer. And the way they assessed the presence of high PSMA expression was by using a specialized kind of PET scan known as Gallium 68 PSMA-11 PET scan. In addition, they made sure that these patients do not have another type of prostate cancer, also call it dedifferentiated prostate cancer, by making sure that those patients did not have a traditional PET scan-positive disease.

So this was a highly selected patient population who were expressing PSMA on their prostate cancer. Prior to this presentation, the earlier presentation had shown that lutetium PSMA was superior to cabazitaxel as far as progression-free survival is concerned and also was associated with lower incidence of grade 3 or 4 side effects. In this update, after a longer follow-up of 3 years, Dr. Hofman and Dr. Davis, who is a senior author, they presented the data on overall survival, which was a secondary analysis, and overall survival was similar with cabazitaxel as well as lutetium PSMA in the range of 19 months. We did not see any new safety signal.

So, what does it mean for us? What does this mean for our patients? My key takeaway message here is, lutetium PSMA is a suitable option for men with metastatic castrate-resistant prostate cancer who are expressing high PSMA on their prostate cancer after they had sustained disease progression after docetaxel. However, cabazitaxel is also a valid option in this setting. I would like to add my own view in addition to this because lutetium PSMA was better tolerated and was also associated with better progression-free survival. In my patients who are progressing on docetaxel chemotherapy, I would like to use lutetium PSMA first followed by cabazitaxel chemotherapy. So that would be my key takeaway from this abstract. Now we can move to the next abstract.

This was also an update, a much longer update, on ENZAMET trial. If you recall, ENZAMET trial was one of those trials which established that deeper androgen blockade, or deeper androgen signaling inhibitors such as enzalutamide, apalutamide, or abiraterone, these trials were conducted in 2015 onwards, and all these trials showed that upfront using deeper androgen signaling inhibitors at the time of metastatic hormone-sensitive prostate cancer onset improved survival. So ENZAMET trial used enzalutamide, and it showed in the first analysis, which was presented by Dr. Davis and Dr. Sweeney in the 2019 ASCO Meeting Plenary session, that adding enzalutamide to androgen-deprivation therapy in patients with metastatic hormone-sensitive prostate cancer significantly improved survival. In this longer follow-up of 68 months, so we are talking about almost 6 years of follow-up, now, these investigators from ENZAMET trial, as presented by Dr. Davis, showed that the combination of enzalutamide with androgen deprivation therapy or testosterone suppression therapy continues to significantly improve survival in patients with newly diagnosed hormone-sensitive prostate cancer or metastatic prostate cancer. One interesting part of this unique aspect of this trial was that patients were allowed to receive docetaxel chemotherapy concurrently to the protocol treatment. And in this trial, 45% patients actually receive docetaxel chemotherapy. So 503 patients exactly out of 1,000-plus patients. So if you look at the subgroup analysis of those patients who received docetaxel chemotherapy, enzalutamide does not seem to benefit those patients from the overall survival perspective.

So on the face of it, it looks like enzalutamide is not helping those patients who are receiving docetaxel concurrently. But there are some caveats with that kind of subgroup analysis. The first one is this is not a randomized assignment of docetaxel chemotherapy. Patients were determined to have docetaxel chemotherapy after discussion with their respective oncologist. This was not a prespecified analysis that so many patients with docetaxel will receive enzalutamide. Also, this was not a randomized assignment of docetaxel. And third, that I don't think this trial had enough power to look for that subgroup analysis.

So my take on this trial is that updated results from this trial, almost 6 years of follow-up now show that enzalutamide continues to improve overall survival with a 30% reduction in risk of death in patients with metastatic castration-sensitive or hormone-sensitive prostate cancer. Furthermore, the effect of enzalutamide, in my view, on overall survival is independent of the receipt of docetaxel. If you look at the whole trial population for which the trial was covered for, enzalutamide improved survival for all patients. And based on these results, I feel more confident in saying that upfront intensification of treatment with deeper androgen inhibition remains a standard of care for our patients with metastatic hormone-sensitive prostate cancer and should be offered to all eligible patients with this condition. With that, I would like to wrap up the prostate cancer abstracts. Thank you very much.

Greg Guthrie: And thank you, Dr. Agarwal. Next up, we will have Dr. Gilligan, who is going to be discussing testicular cancer.

Dr. Gilligan: Thank you very much. So I have 2 studies I want to talk about and then just give a headline of some interesting things that I think are kind of coming down the road. Both of these abstracts have to do with improvement over time in specific patient populations we used to worry about. I'm not saying we don't worry about them anymore, but things are looking better now than they had 1 or 2 decades ago. So the first topic addresses late relapses in testicular cancer. And historically, we have been concerned that these patients did worse and had worse outcomes. And late relapse could variously be described as after 2 years or after 5 years. In the current study, they defined late relapse as being after 2 years and very late relapse as being after 5 years. And what was special about the study was that it captured the entire population of patients with testis cancer in Norway and Sweden so that it wasn't based on a center of excellence that gets selective referrals. It was actually a population-based study. And the key conclusion of the study was one I found, once again, that late relapses are rare. So for stage I patients, 2% of patients will relapse after 2 years, 1% after 5 years, and 0.5%, so 5 out of 1,000 patients, after 10 years. So if you're 2 years out, the likelihood of a relapse is quite low.

And if you're 5 years out, it's half of that. In patients with metastatic disease, similarly, 3.6% relapse after 2 years, 1.6% after 5, and 0.8% after 10 years. And what was interesting to me was that if you looked at the more recent patients who were diagnosed after 1995 - I know that doesn't sound very recent, but they had even earlier patients also in the study - the very late relapse rate almost resolved and went away. It went from 2.2% all the way down to 0.8%. So I think with modern imaging, modern care patterns, we're seeing less of this than we used to. But overall, patients were doing better even if they do relapse late.

One thing that was interesting in the study to me also was for stage I disease, we typically recommend surveillance rather than active treatment. So active treatment with non-seminomas would be a retroperitoneal lymph node dissection or more surgery or chemotherapy. With seminoma, it would usually be chemotherapy or radiation, although surgery is being investigated there now. And they did find that in men who chose surveillance, which we still recommend, the late relapse rate was a little bit higher, but it was still affecting a small percent of patients. So the relapse rate beyond 2 years was 4% rather than 1%, but out of 4,000 patients, there were only 3 deaths from late relapse. So this isn't changing the recommendation for surveillance, but it is an alert that patients who are on surveillance for stage I disease have a slightly higher risk of late relapse and that may affect how we follow them and specifically how long we follow them. One of the things that was interesting in the study is in the United States, we often stop scans at 5 years, but in the SWENOTECA countries, they continue scans all the way out to 10 years. I don't know that U.S. guidelines are going to change, but it was a provocative finding.

The key thing, as I alluded to at the beginning, was that 61% of patients with late relapse were alive 10 years later, and while we would like that number to be higher, it used to be around 50% in older studies. So it's a significant improvement from where we were before. A particularly interesting thing to me was that patients relapsing 2 to 5 years out actually had the best prognosis. Patients who relapsed in years 1 to 2 had a worse prognosis and patients relapsing after 5 years had a worse prognosis, whereas the patients relapsing 2 to 5 years had a better prognosis. In the end, I think what this means for us is that patients are doing better. It's not going to really change our treatment patterns, but it's reassuring that we shouldn't be pessimistic about late relapses, and we still have a solid chance of curing them. So again, bottom line, most men with late relapse is cured and late relapse is less common now than it was earlier, particularly in non-seminomas.

Let's go to the next study. So this is a different group of patients who had a particularly ominous prognosis historically and still we have a lot of room for improvement. These are patients with non-seminomas that start in the mediastinum. So in the chest, under the breastbone, under the sternum typically. And patients are treated aggressively upfront, they are considered poor risk at the initial time of diagnosis, and they're treated aggressively at the time with 4 cycles of BEP or 4 cycles of VIP chemotherapy. And then they go for surgery to remove any residual disease. And the hope is they're cured at that point because historically, if there was a relapse after chemotherapy and surgery, it was almost impossible to cure them. Indiana University published their results using high-dose chemotherapy in this population, and they reported that 30% of men who were treated with high-dose chemotherapy had no evidence of cancer after 2 years, and 35% were still alive.

Obviously, we need longer follow-up, but most of the relapses you're going to see are going to be in the first 2 years. So while again, there is significant room for improvement here, this indicates that high-dose chemotherapy is a good option, and that has been a question. So this is reassuring in that regard. But it is a good option for men with relapsed mediastinal non-seminomas of the germ cell tumors. So there's hope there where in the past, this has felt a little bit helpless.

The thing I wanted to also highlight was that there are 3 things I think are going to be interesting to keep an eye on over the next year. One is the use of surgery for early-stage seminomas. There are a number of papers out about that. I still think this is an investigational approach, and so I didn't want to go into great detail about it, but it is looking like that RPLND, or retroperitoneal lymph node dissection, will likely or may be an option for stage I and stage II seminoma in the future. We are getting more evidence for that. It's not quite as promising as we had hoped until there's more data that's needed, but it's looking like that will become an option. So for men with early-stage seminoma, at least raising the question whether surgery is an alternative to chemotherapy or radiation, is an important discussion to have with your oncologist.

Secondly, MRI rather than CT scans for surveillance. So to keep an eye on men who have been treated or men who are just stage I and are being followed and typically come in routinely for CT scans, which expose people to ionizing radiation, which theoretically has a risk of causing cancer, there's more and more data that MRI is just as good as CT, and MRI does not use ionizing radiation. So there's probably going to be an expanding role for MRI as an alternative to CT scans.

And lastly, the use of microRNA rather than just depending on serum tumor markers. So right now, we use the blood tests alpha-fetoprotein, beta hCG, extensively to monitor for relapse, and there's more and more evidence for using what we call microRNAs instead. It may be more accurate in multiple different settings. So it'll be interesting to see how that evolves and that's what I wanted to cover today. Thank you very much.

Greg Guthrie: Thank you, Dr. Gilligan. And now we have Dr. Grivas, who's going to discuss some research in bladder cancer.

Dr. Grivas: Thank you so much, Greg, and thanks Cancer.Net for the great opportunity to discuss this for our patients. We're very excited about the data from the ASCO Annual Meeting, and I would encourage the audience to review as possible other presentations as well. I'm going to cover 3 highlights. I'm going to start with the QUILT-3.032 study. This trial reported the final results of a clinical trial that took place in different centers and involved patients with what we used to call "superficial bladder cancer." And the modern term is "non-muscle-invasive bladder cancer." Bladder cancer that does not involve the muscle layers, not that deep in the bladder wall. Non-muscle-invasive bladder cancer is usually treated by our colleagues in urology with installation inside the bladder with an older form of immunotherapy which is BCG. And that's the most common way we treat this disease. And proportion of patients may have tumors that may not respond to BCG that may come back or persist despite the installation of the BCG in the bladder.

And these patients usually have a standard of care of getting what we call radical cystectomy, meaning, removal of the bladder and the lymph nodes around the bladder, radical cystectomy and lymph node dissection. However, many patients may not have, I would say, the opportunity to get the surgery because the body may not be that strong to undergo that significant procedure. Very few patients may have that challenge because of other medical conditions or what we call poor performance status. Or some patients for quality-of-life reasons may try to keep their bladder as long as possible. And for some of those patients, that might be an option.

And we have been looking for those options in the last few years. Intravesical, inside the bladder, installations of chemotherapy have been used with some positive results in some other studies. So that's an opportunity. We call this intravesical, inside the bladder, installations of chemotherapy, and the other option is an FDA-approved agent given intravenously inside the vein called pembrolizumab, which is in the form of immunotherapy. Of course, research continues. And this study I'm showing here from Dr. Chamie and colleagues, looked at this combination of BCG plus this molecule called N-803. This is another form of immunotherapy, and this was tested in patients who have this BCG-unresponsive, as we called it, non-muscle-invasive bladder cancer. The results were very promising. I would say impressive that it was a high response rate if we focus our attention on patients who had the superficial form carcinoma in situ, about 70% had no evidence of cancer upon further evaluation of the bladder. And in many of those patients that this response lasted for more than 2 years. 96% of patients avoided to have worsening of the bladder cancer in 2 years for those who had a response, and about 9 out of 10 avoided cystectomy again from those patients who had received the response. So it was 70% of all the population.

And as you see, all patients, 100% were alive without dying from bladder cancer after 2 years, which again is a very promising finding. This combination, to conclude, this inside the bladder installations of BCG plus the N-803, looks very promising. For those patients with BCG-unresponsive non-muscle-invasive bladder cancer, that might be an option down the road, we have to see.

Now I'm going to shift my attention to patients with metastatic or spread urothelial cancer. I want to point out that I'm a co-author in this abstract and I participated in that survey I will show you the results from. This is a population of patients who have spread cancer from the urinary tract, either the bladder was the most common origin or other parts of the urinary tract, for example, what we call kidney, pelvis and ureter, or rarely the urethra. The urothelial cancer that starts from those areas, again more commonly bladder, if it spreads, if it goes outside the urinary tract system, usually those patients get chemotherapy, what we call with an agent called cisplatin if they can tolerate that chemotherapy drug or carboplatin if they cannot tolerate the cisplatin drug. And usually either of these, cisplatin or carboplatin, is combined with a drug called gemcitabine. That's the most common chemotherapy used as initial therapy for patients with spread metastatic urothelial cancer. In this abstract, Dr. Gupta and colleagues tried to survey 60 medical oncologists, including myself, who treat urothelial cancer that considered experts in this disease type, to see if there are any features that could deter us from using chemotherapy in those patients. In other words, are there any features that may make us think that chemotherapy may be too risky for our patients and we should not do it? We should give immunotherapy instead.

This is probably a small proportion of our patients, maybe 10 to 20% in our practice, may not be able tolerate that chemotherapy. And which are those features? Poor performance status, meaning the body is very tired and the patient is not moving too much, is confined in the chair or the bed most of the day, and rely on others on daily activities. This is what defines the performance status of ECOG 3. Peripheral neuropathy, meaning that there is numbness or tingling or weakness in the hands or the feet that impact the quality of life. And patients may have trouble buttoning buttons or tying laces, so impacting the quality of life. That's grade 2 neuropathy. Symptomatic severe heart failure, there is a grading system, like New York Heart Association Class III or IV that is significant, notable heart failure symptoms. And also, patients with kidney failure with what we call creatinine clearance below 30 cc per minute. That's a marker how we measure kidney function and the creatinine clearance more than 60 is usually close to normal. As the creatinine clearance drops and goes below 30, chemotherapy with these platinum agents may become a challenge by itself or if it's combined with the ECOG performance status of 2, which means more patients are not moving most of the day.

So those features again have to do with the functionality of the day-to-day life. The presence of significant neuropathy, heart failure, and poor kidney function may potentially make the oncologist recommend immunotherapy versus the standard of care, which is chemotherapy, in those patients. And I would say if someone gets chemotherapy, which is the majority of patients, usually they may get immunotherapy later. So pretty much I would say discuss with the medical oncologist what is the right treatment for you. Most patients get chemotherapy up front, followed by immunotherapy. Some others may need to get immunotherapy, and those criteria help us make that patient selection for the right treatment at the right time.

So I just alluded to you that most patients with spread or metastatic urothelial cancer, most of them receive chemotherapy. We discussed some criteria in the previous studies that we may use immunotherapy upfront instead of chemo, but for the vast majority of patients, chemotherapy is used upfront and that was based on the results of phase 3 clinical trial called JAVELIN Bladder 100. This was presented at the ASCO Annual Meeting in 2020 about 2 years ago, and it was published in a big journal. And that study showed that if you give chemotherapy upfront, those patients who can tolerate the chemotherapy, of course, who do not have the previously listed criteria, those patients benefit and live longer, so longer overall survival, meaning they live longer, and they have longer progression-free survival, meaning they live longer without worsening of the cancer if they get immunotherapy with, immunotherapy drug is given through the vein, called avelumab.

If that is given after the end of chemotherapy for patients who have a response or stable disease, meaning no progression on chemotherapy. So if you get a complete response, meaning that the CAT scans look normal after chemotherapy as at least we can tell visually. Partial response, meaning that the CAT scans look better, but still we can see some cancer spots. Stable disease, meaning that the scans look stable compared to the beginning before we start chemotherapy. If someone has worsening of the cancer in chemotherapy, then the concept of maintenance therapy doesn't apply. So it's only for patients with complete response, partial response, or stable disease, SD.

And the poster we had, and I can tell you - I was a co-author in the abstract and co-investigator in the trial, as a disclosure - was sort of the benefit of the patient with avelumab as maintenance therapy after chemotherapy was notable in patients with complete response, partial response, and stable disease. So in any of these 3 categories, avelumab immunotherapy should be offered as level 1 evidence and benefit patients in terms of overall survival and progression-free survival as long as there's no progression to the upfront initial chemotherapy of the patient with metastatic urothelial cancer received. Many other abstracts on these cancers were presented, and I would encourage you to look at them. Thank you so much for the opportunity today.

Greg Guthrie: And thank you, Dr. Grivas. Next, we have Dr. Zhang who will discuss some research in kidney cancer.

Dr. Zhang: Hi everyone, glad to be here today. I'll be discussing 2 highlights from ASCO 2022 in kidney cancer. The first one we wanted to highlight was a trial called EVEREST: everolimus for renal cancer ensuing surgical therapy, a phase 3 study. And in context, this study is a trial of evaluating everolimus, an mTOR inhibitor, in the post-surgical context. And we do have in the landscape 2 approved therapies, sunitinib and pembrolizumab. And as we have seen, some effective therapies in the refractory setting, many of these therapies are being tested in this postoperative space. So this particular study of EVEREST looked at patients with renal cell carcinoma who underwent resection for their primary nephrectomy and looking to evaluate postsurgical treatment. So everolimus has been approved as a treatment on its own in the refractory setting as well as in combination with lenvatinib. And so this question of whether everolimus alone could delay or prevent disease recurrence in the postoperative setting was tested in this EVEREST trial. The study ultimately enrolled more than 1,500 patients and assigned them to receiving either everolimus or placebo in the postoperative setting. Of these patients, 83% had clear cell kidney cancer and the remaining had non-clear cell kidney cancer. And the follow-up was quite long, over 5 years, and actually over 6 years, and the researchers looked at time until disease recurrence. And risk of recurrence was actually decreased by 15% in patients who were treated with everolimus compared to placebo.

But the prespecified cut-off for a statistical significance was not quite reached, and the researchers took a specific look at a group of very high-risk patients defined by larger tumors, invasion of the perinephric fat in renal veins or invasion of nearby organs or known positive disease. And those patients with very high-risk disease had more benefit from everolimus compared to placebo. Of note, 37% of patients who were treated with everolimus had to stop treatment due to their side effects, and the most common severe side effects included mouth ulcers, high triglyceride levels, and high blood sugars. So ultimately this particular study did not show sufficient benefit of everolimus given the toxicity and lack of statistical significance. And so this is a balance between potential benefit in delaying recurrence versus treatment toxicities that we must have in this adjuvant setting.

So what does this particular study mean for patients? Well, it was certainly a large phase 3 trial performed in the cooperative group setting and through the generosity of 1,500 patients and the principal investigators on the study, we learned this answer for a very important question of whether everolimus makes a difference in this postoperative setting. I think we're not using this in clinical context currently, but in this postoperative setting, we are always balancing this risk of toxicity with the potential for benefit and discussing the potential treatment options. I do not think this particular trial changes the standard of care in this adjuvant setting.

And then I think finally for today's prepared talks, this abstract on depth of response and association with clinical outcomes with CheckMate 9ER patients treated with cabozantinib and nivolumab. So this was a post-trial analysis of patients who had kidney cancer with disease spread and treated with cabozantinib and nivolumab compared with sunitinib in the CheckMate 9ER study. And the context, this was the phase 3 trial in which the benefit of cabozantinib and nivolumab was established in the first-line setting and gained the registration and approval of this combination in the first-line treatment of metastatic kidney cancer. This particular analysis, presented at ASCO this year, was a post-trial prespecified analysis evaluating this depth of partial responses and associating those with clinical outcomes of time until disease progression as well as time until death.

These depth of responses were defined as 80 to 100% for PR-1, 60 to 80% for PR-2, and then 30 to 60% as PR-3. And as we saw in this analysis, the deeper the responses on cabozantinib and nivolumab, the more correspondence with higher 12-month rates of disease-free progression compared with those same depths of responses from sunitinib. And there were similar 12-month overall survival rates for patients with similar depth of responses for either the cabozantinib and nivolumab combination compared with sunitinib. So I do think the degree of partial response in these settings is productive of time until progression and establishes further the efficacy and benefit of cabozantinib and nivolumab compared with sunitinib. And what does this trial mean for our patients? I think that early on, as we're looking for responses and radiographic changes for our patients on cabozantinib, nivolumab in the first-line setting, these deeper responses are associated with longer time until disease progression, and we can counsel patients, to discuss whether cabozantinib and nivolumab is working for them. This could be an early indicator for how patients will do overall on this combination. So with that I'd love to wrap up and turn it back over to you, Greg.

Greg Guthrie: Thanks so much Dr. Zhang. And now it's time to move on into our Q&A session.

This is for you, Dr. Agarwal. So the question is utility of triple therapy, ADT plus docetaxel plus ASI and metastatic hormone-sensitive prostate cancer given ENZAMET was inconsistent with PEACE-1 and ARASENS. Would you give ASI concurrent or sequential after chemotherapy for tolerability? I'm assuming ASI here is androgen suppression, correct?

Dr. Agarwal: Yes. Great question. There are 2 questions here. Number 1, if I would use triplet therapy given the negative subgroup analysis of the ENZAMET trial, and number 2, what is the role of triplet therapy in general? The answer to the first question is ENZAMET trial, subgroup analysis is very different from preplanned, prespecified, well-powered analysis from PEACE-1 and the ARASENS trial. So yes, we saw discrepant results, but my impression from ENZAMET trial is enzalutamide is an effective option for all patients regardless of the receipt of docetaxel chemotherapy because that was a subgroup analysis. So I don't think it really affects negatively the results of the ARASENS and the PEACE-1 trial. But a bigger question here is triplet therapy versus doublet therapy? Is triplet therapy for all or doublet therapy for all? Answer is no. Triplet therapy trials only showed that adding a novel hormonal therapy or deeper androgen blockade to the backbone of ADT plus docetaxel improves survival.

These trials did not answer the question, if adding docetaxel chemotherapy to ADT plus, for example, enzalutamide or darolutamide or apalutamide, will improve survival. We do not have that question answered by any of the trials and unlikely any other trial will answer that question. So my take ADT plus docetaxel is replaced by ADT plus docetaxel plus these deeper androgen blocker therapy. So wherever I was going to use docetaxel chemotherapy, so those are the patients with visceral metastases or in my practice, when I do comprehensive genomic profiling, I see those molecular aberrations which predict lack of response to deeper androgen blockade such as baseline AR variants. Or if I see 2 out of 3 mutations of p53, RB loss, p10 loss, if I see 2 out of these 3, I tend to think about docetaxel chemotherapy. So in those patients where I'm using ADT plus docetaxel, I would add another androgen receptor blocker such as abiraterone and darolutamide. But when I'm using enzalutamide or apalutamide which I use for majority of those patients, my patients with metastatic hormone-sensitive prostate cancer, I do not think about triplet therapy.

Greg Guthrie: Thanks, Dr. Agarwal. We actually have a follow-up question, and this is, what is the role of oncology in low-stage early prostate cancer? Can neoadjuvant chemotherapy reduce the number of people who end up with metastatic prostate cancer?

Dr. Agarwal: This answer is very simple. There is no role of neoadjuvant chemotherapy in high-risk localized prostate cancer or any localized prostate cancer setting.

Greg Guthrie: Great. Thank you. Next question. I believe that this is for everybody. How long will it be until the information from the trials discussed will be used in the community clinics? What can patients do to bring this information to their less experienced doctors?

Dr. Grivas: So, Greg, just to clarify the question, is it about the translation of the results of the clinic from ASCO to clinical practice, generically speaking, or any particular tumor type or any particular data results?

Greg Guthrie: The way I read this question, it's more just kind of a broader scope question about just like, how long does the results of clinical trials make it to community practice, and what role can patients have in perhaps fostering this transmission of information?

Dr. Grivas: Of course, I can start briefly, and then my colleagues can add. I would say the world we live in right now, the information travels very quickly. It's much faster compared to the past. And I think there is much more alignment, in my opinion, in terms of information access between academic oncologists and community oncologists. If, for example, a trial result comes at ASCO being presented, and then there's a follow-up approval authority from a regulatory agency, this agent may be accessible to both community and academic practices. Of course, there are always opportunities for education, and Dr. Agarwal is the director of the ASCO Daily News, and he knows that well to disseminate the information well, broadly, in an equitable manner across academic oncologist providers and community providers. And I think CME, continued medical education practices, can help in that regard. And obviously, the other aspect of that is the ongoing clinical trials and how we can do a better job disseminating the opportunity for equitable participation in clinical trials across racial groups, ethnicity groups, minority groups, to give them the chance to participate in ongoing clinical trials that may change the practice down the road, which are just early thoughts. But other colleagues can comment.

Dr. Zhang: Yeah, if I could chime in. I think these continuing medical education programs, particularly in the context after large symposia like the ASCO Annual Meeting we just had, are particularly important. And the Best of ASCO series, as well as ASCO Direct Highlight series - I believe Dr. Grivas and I are hosting 2 of these - are very helpful, I think, to bring the latest findings from the ASCO Annual Meeting to our community colleagues. And they really are our colleagues. We work together with our oncologists within the community to take care of our patients, oftentimes for standard of care treatments. Patients can access them more in their backyards.

And I think from a patient standpoint on the second part of the question, they're able to hear these from patient-friendly platforms and to bring that to the attention of their oncologist, wherever that may be. It all helps in the grand context of clinical care. So I hope that these trial results and the latest findings from ASCO can get inseminated very quickly.

Dr. Grivas: And to also add very briefly, the role of patient advocacy groups, and in the bladder cancer work, there are many, for example, the Bladder Cancer Advocacy Network, World Bladder Cancer Coalition, and many others can help also in that regard and teaming up with all of us to disseminate information and also clinical trial access.

Greg Guthrie: Great. Thank you, everyone. We have a question for Dr. Grivas. After the survey results in the study you described, is there any plan to make a guideline or tool to make sure we standardize the definition of cisplatin/platinum ineligibility?

Dr. Grivas: Great question. Just 1 more thing on my prior answer, kudos to Cancer.Net for serving that mission, Greg and Claire in that-- or the previous question to have a complete answer. Answering this new question here, which is very important. I think the next step is to try to publish the results of the survey. The survey like the previous one done by Dr. Galski about 10 years ago-- it's a survey on expert oncologists, and it's a consensus-based definition. It's criteria that we came up with together. And I think the next step here is to publish this in a peer-review process. And our hope is by publishing these results, we can have a more formal definition to help guide our practices in academia, but also in the community oncology practices and make sure that we have a standardized way that we approach this therapy selection and of course, to help design clinical trials that for this particular patient population in order to improve outcomes in this setting. So hopefully publication will come soon.

Greg Guthrie: Thanks, Dr. Grivas. I'll just drop a really quick pitch there. Here at Cancer.Net, we do have a very broad array of information on clinical trials. And patients can come visit us at Cancer.Net and learn about clinical trials, what they mean, and how they help advance cancer research. We now have a question for Dr. Zhang. Based on the results of EVEREST and other trials approved systemic therapies in the adjuvant setting like sunitinib and pembrolizumab, are there ongoing other trials in this setting and is risk stratification used?

Dr. Zhang: The short answer is yes. There are ongoing adjuvant trials that build on pembrolizumab in the adjuvant setting. There's one that is looking at the addition of belzutifan with pembrolizumab in the adjuvant setting. So that trial is a global trial which is about to get started, if not enrolling already. And in the context of adding on in the adjuvant setting, I do think we really need to discuss with our patients how much of a benefit the treatment will have versus the real toxicity in the postoperative setting, many patients will not have symptoms from their cancer, so they may have some pain or healing side effects from surgery, but they won't have symptoms from cancer. So any toxicities from medications can be further amplified, so are we truly giving a lot of benefit in that context or not. So that's an individualized decision, and I do think conversations must be had to make that decision together.

Greg Guthrie: Thanks, Dr. Zhang. I want to ask a question myself of Dr. Gilligan. You had mentioned that microRNA is an emerging field of study, and I've heard about this in other types of cancer as well. I wonder if you could discuss that a little bit more.

Dr. Gilligan: Yeah, microRNA, the promise that holds is being a more accurate detector, specifically of testicular cancer. So the problem we have with alpha fetoprotein and beta HCG is half of the testicular cancers may not make 1 or both of those markers. So people can relapse without the markers going up, even though markers are most commonly what we see, there are a couple of different scenarios. Someone has stage I testicular cancer, which means their testicles removed and all their scans show no evidence of cancer. We know that 25% or so of non-seminomas and 20% or so of seminomas will relapse, even though we can't see what the cancer is, and the markers are negative in that situation. MicroRNA may be able to detect those people who still have cancer much, much earlier. So we know that they're, in fact, not stage I and that they need active treatment right away. So that's one place. Another place that we're seeing evidence is that men who've had metastatic testicular cancer. They go through chemotherapy, and they have residual masses. And we're wondering if there's cancer in those masses or is it all dead scar tissue or is it teratoma? MicroRNAs may be able to allow us to determine who needs additional treatment, who needs surgery without having it. Right now, we typically go in and operate just to figure that out.

So there are a number of situations in which we could more accurately stage patients and figure out who's cured and who's not cured much earlier in the course of disease. And for a patient, this would be fantastic, because right now, if you've got stage I disease with non-seminomas and you go on surveillance and somebody says you have a 25% risk the cancer is going to come back, that's a 1 in 4 chance that at some point in the next 2 years, most likely, or longer, you're going to have to suddenly drop everything and go through months of chemotherapy. If we knew on day 1, it looks like you're cured, but in fact, there's cancer hiding there somewhere, and we need to treat you now, that would be helpful to know so they can get it over with. And the other men, we could say we're really extremely confident that there's not a 25% risk, it's a 5% risk or something much lower. So there are a number of ways, if this really gets proven and there's emerging data that's promising, I think we could reassure men, treat them more appropriately, spare them unnecessary treatment, and give them more peace of mind.

Greg Guthrie: Great. Thanks, Dr. Gilligan. I think we have a question from Dr. Grivas now.

Dr. Grivas: Thank you, Greg. This is a great panel. I like to learn from my colleagues here. One question for Dr. Zhang, you have done so much work in the field, leading the field there, Dr. Zhang. Any comments about the ideal end points in the adjuvant setting in kidney cancer, urothelial cancer, disease-free survival or overall survival? Would you comment about how we design trials, and what will be an acceptable benchmark? And what is meaningful for patients, too, in the adjuvant treatment after radical surgery for kidney cancer and urothelial cancer?

Dr. Zhang: Oh, that's a great question, Petros. Thank you so much for asking. We have discussed this many times together because you and bladder cancer and myself and kidney cancer, we're thinking a lot along the same lines right as new immunotherapies get approved in the postoperative setting, so disease-free survival as an endpoint and recurrence-free survival as an endpoint is a valid endpoint. It's a direct result of the randomized treatment on the trial, so I do think that is the valid endpoint, and it's an endpoint that the FDA has approved the sunitinib and pembrolizumab indications in kidney cancer, nivolumab and bladder cancer. So I think it's certainly a valid endpoint to delay disease recurrence. How much of that is meaningful degree of improvement for an individual patient? Their own measure of recurrence is either yes or no. It's much more binary than population effects. So how much does that translate into benefits for the patient? I think that warrants deeper individualized discussion. But these disease-free survival endpoints in all of these studies is a valid endpoint to see whether the treatment is worthy in delaying disease recurrence in each of these disease types.

Greg Guthrie: Thanks, Dr. Zhang. We have one last question here, and I believe this is a follow-up for Dr. Gilligan. And what is the time frame for the rollout of microRNA 371 to the community?

Dr. Gilligan: I don't know the answer to that. I'm not sure that we have enough data right now that it's going to get approved. I think we're headed in the right direction, but it's very hard to know what the timing of that is. There are trials going on, so I don't know at the moment of exactly what the scenarios are in which people are going to be, which patient populations are going to be eligible, but there are trials going on. I think I'm hoping within the next 2 years or so, but I really don't know what the time frame is, unfortunately.

Dr. Grivas: And if I may add a more generic comment to Dr. Gilligan's wonderful answer is that when we have what we call biomarkers that are like metrics that can give us information about how the patient does over time, it's important to tease out what we call prognostic, meaning how can this biomarker give us a sense of the chance of recurrence, as Dr. Gilligan said, or death from the cancer. But also, the bigger question is, is it going to give us information to predict benefit from an individual therapy? And that's a bigger question in oncology that is a harder one. This predictive question and try to identify biomarkers and validate them to make sure they have, they're clinically useful. They can help us make treatment decisions in the clinic. And I'm very excited about what Dr. Gilligan discussed about the promise in the future. But more trials are needed for many biomarkers.

Dr. Gilligan: I think when we do this update next year, we'll have significantly more data then, I'm hopeful.

Greg Guthrie: Thank you to you all. Thank you, Dr. Agarwal. Thank you, Dr. Grivas. Thank you, Dr. Gilligan. Thank you, Dr. Zhang, for sharing this great research with us, as well as your expertise. It's been a real pleasure this afternoon. And to all of our viewers, thank you for joining us. You can find more coverage of the research from ASCO Annual Meeting and other scientific meetings at the Cancer.Net blog, which is at www.cancer.net/blog.

And if you're interested in more Cancer.Net content, please sign up for a monthly Inside Cancer.Net newsletter or follow us on social media. We're on Facebook, Twitter, and YouTube where our handle is always @CancerDotNet, with dot spelled out. Thank you all, and be well. Thanks.

ASCO: Thank you, Dr. Agarwal, Dr. Gilligan, Dr. Grivas, and Dr. Zhang. You can find more research from recent scientific meetings at www.cancer.net.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, members of the Cancer.Net Editorial Board discuss new research in molecular testing, also known as biomarker testing or tumor marker testing, to help guide treatment for people with early-stage non-small cell lung cancer. This podcast is led by Dr. Ryan Gentzler, Dr. Xiuning Le, Dr. Brendan Stiles, and Dr. Vamsidhar Velcheti.

Dr. Gentzler is the director of the Thoracic Oncology Clinical Research Program at the University of Virginia (UVA) and chairs the UVA Cancer Center's Lung Cancer Translational Research Team.

Dr. Le is an assistant professor in the Department of Thoracic/Head and Neck Medical Oncology in the Division of Internal Medicine at The University of Texas MD Anderson Cancer Center.

Dr. Stiles is chief of thoracic surgery and surgical oncology at Montefiore and Albert Einstein College of Medicine.

Dr. Velcheti is the director of thoracic medical oncology at New York University Langone's Perlmutter Cancer Center.

View disclosures for Dr. Gentzler, Dr. Le, Dr. Stiles, and Dr. Velcheti on Cancer.Net.

Dr. Gentzler: Thank you, everyone, for joining us. We've got a great group here today, and we're really going to focus on talking about molecular testing in lung cancer. This is a very hot topic. My name is Ryan Gentzler from the University of Virginia. I'm a thoracic medical oncologist. We have Drs. Le, Stiles, and Velcheti with us today. I'd like them to go ahead and introduce themselves, starting with Dr. Le.

Dr. Le: My name is Xiuning Le. I'm an assistant professor. I'm at the MD Anderson Cancer Center here in Houston, Texas. I'm also a medical oncologist. Thank you, Ryan, for inviting us today.

Dr. Stiles: Hey, everybody. I'm Brendan Stiles. I'm a thoracic surgeon. I'm chief of thoracic surgery at Albert Einstein College of Medicine in Montefiore Health System here in the Bronx in New York.

Dr. Gentzler: All right, thanks for joining us. And Dr. Velcheti.

Dr. Velcheti: Thank you, Ryan. I'm Vamsidhar Velcheti. I'm the director of the thoracic oncology program at NYU.

Dr. Gentzler: All right, great. We hear a lot of terms thrown around about molecular testing, genomic testing, biomarkers, oncogenic drivers, and I thought it would be good to just define what exactly is molecular testing, so all of our listeners are aware of what we're talking about. Dr. Le, do you want to take this question?

Dr. Le: Yeah. So we have many terms, as you described. In my eyes, there are 2 sets of testing, and then some of them also classify into actionable versus not actionable. So for clinical use, we usually ask the tumor to be tested for both the mutations as well as the immune marker. Usually, the panel of mutational testing is more than a field. Usually, it's depending on the platform we're using, oftentimes in the hundreds of things. And then the immune markers, usually, we refer to PD-L1 and the tumor mutational burden. Those are the 2 commonly used markers now in the clinic. Some of those markers, especially the hundreds in gene testing, not all of them can lead to a clinical decision because we're still in the phase of understanding the interactions of different genes. However, there is a subgroup of those mutations. Nowadays, we have targeted therapy for, we call those actionable mutations. So in the clinic, we push for testing for a panel of mutations as well as immune markers, hoping to look at the tumor comprehensively so that we can recommend a good treatment regimen precise to that particular tumor, precise to that particular patient.

Dr. Gentzler: Yeah. Wonderful. This has also been termed precision medicine, where we really match a therapy to a specific genomic abnormality identified on these tests and maybe, Dr. Velcheti, if you could maybe elaborate on some of the different ways that these tests are performed and how we're using these in clinic today?

Dr. Velcheti: Yeah, definitely. I think our understanding of the biology of lung cancer has evolved quite dramatically over the past several years and obviously it's led to a lot of advancements in terms of treatment opportunities for patients. Broadly, the way I look at biomarkers in lung cancer or, for that matter, any cancer, it's like you have biomarkers that actually kind of give us very deep insights into the biology of the cancer and giving us insights into how aggressive somebody's cancer is. Those are called prognostic biomarkers, kind of predicting outcome. And there are predictive biomarkers where there are certain biomarkers. If you do have some of these biomarkers in the tumor, then you could potentially use certain treatments that might work better for patients who have those biomarkers. So now we have a lot of different approaches in terms of how we kind of test for these biomarkers. Especially in lung cancer, now we have a lot of new therapeutics for certain genomically categorized types of lung cancer.

And the challenge now is that we have so many different mutations we absolutely need that information to decide on treatment. So how do we test that? Until a few years ago, we've been doing a single gene testing. The problem with those approaches is that we have so many different genes we need to test and we kind of do sequential gene testing, a single gene testing, we won't get all the information we need to make the right decision for our patients. So the standard approach in most oncology practices, especially larger cancer centers and academic medical centers, is do comprehensive genomic profiling, and that's being widely accepted as a standard approach right now.

Dr. Gentzler: Wonderful. And this has really been something that has fallen on the laps of thoracic medical oncologists as we've treated patients with advanced stage or stage 4 disease. And this is starting to become more and more important and relevant for surgeons. And Dr. Stiles, I just wanted to bring you into the conversation and see if this is something that, prior to some of the more recent data, which we'll discuss in a minute, is this something that as a surgeon, you've kept up with and think it's important in a surgical practice?

Dr. Stiles: Yeah, definitely, Ryan. And I think now is probably the most exciting time for that, right? We used to just be sort of in the prognostic side, like Vamsi said, but now we really are in the predictive side in the early-stage disease. And I think that's why everybody is so excited. But that's why there's now this pressure about the timing of biomarker testing. What do you get? Do you get a whole panel? As we'll talk about some of the trials that have made their way into earlier stage disease, but it becomes inherent upon surgeons to really think about this and understand this, from the first time that they meet the patient I think, as we increasingly get better therapies in earlier stage disease.

Dr. Gentzler: So as this has moved into earlier stage disease, a lot of this has been driven by some new data from clinical trials, and Dr. Velcheti, I thought maybe you could comment on the IMpower010 trial and its relevance and why molecular testing is important in the context of that trial.

Dr. Velcheti: Yes, absolutely. I think the IMpower010 Trial is certainly a new shift in our approach to treating stage I, II curable non-small cell lung cancers. So we haven't had an approval in the adjuvant setting in a while. I mean, of course, we had approval with the osimertinib result of the ADAURA trial, but that's only for EGFR patients. Now we have approval for using immunotherapy in the postoperative adjuvant setting for patients with any level of PD-L1 expression. So this is a large randomized study looking at the role of adjuvant atezolizumab, which is a PD-L1 inhibitor in patients who have PD-L1 expression greater than 1%. Patients were randomized getting platinum doublet alone, which is a standard-of-care adjuvant assistant therapy for patients at stage I, II lung cancer. It is atezolizumab at a dose of 1,200 milligrams given every 3 weeks. Patients who received atezolizumab had significantly improved outcomes in disease-free survival. And the benefit was actually really striking for patients who had high PD-L1, patients with PD-L1 testing TPS score of greater than 50%. They had a really remarkable increase in terms of disease-free survival for those patients. So this is certainly very encouraging. And of course, we know it's now approved. We are still awaiting some overall survival results to mature. But given the extent of the benefits we're seeing with the disease-free survival, I think it's a very promising approach.

Dr. Gentzler: Yeah, so obviously, immune therapy has had a tremendous benefit in the adjuvant setting from this trial and still some longer-term follow-up that's needed. But I think the important point here is that molecular testing may identify certain mutations that may make patients less likely to benefit or respond, or perhaps there's more appropriate treatments than immunotherapy within this group. And that brings us to the next trial that I think really shifted this discussion stage with the ADAURA trial. Maybe Dr. Le, if you could summarize this trial and give us your thoughts on why molecular testing is so important in the era of ADAURA.

Dr. Le: Yeah. So ADAURA trial is also an adjuvant trial, meaning that the patient received additional treatment after the completion of surgery. So ADAURA trial looked at patients who have EGFR mutations. So it's a different biomarker. It's a gene biomarker, not the immune biomarker. So this is a large international trial, enrolled almost 700 patients and then randomized the patients after surgery, after standard chemo, the patient can go on to either receive 3 years of osimertinib, which is the standard-of-care therapy for EGFR mutant patients for metastatic setting, or the control group if the patient just received standard of care, which is to continue the monitoring. The trial actually showed that for people who had osimertinib before that prolonged time of 3 years, the risk of the disease coming back is almost 5 times lower than the patient who did not receive therapy. So based on that really striking benefit of after surgery, after chemotherapy, continue osimertinib in EGFR patients, FDA approved after the surgical resection and all the standard care patient can go on for osimertinib for a prolonged time, which we think currently the data is saying the disease is more likely not to come back. And hopefully, in the future, that result will translate into overall survival benefit.

Dr. Gentzler: Okay, wonderful. And I think both of these trials, both the ADAURA and the IMpower010, are adjuvant trials. So these are trials that allow us adequate time to do molecular testing on a large surgical specimen, formulate our plans, and implement those plans up to a month or longer after surgery. Obviously, there's some new data that we've seen in a press release from the CheckMate 816 trial. This is a neoadjuvant trial of chemotherapy plus nivolumab. We've seen previous data from this trial showing some results, but this moves the conversation into the neoadjuvant space, and Dr. Stiles, I wonder if you could give us a summary of your thoughts on the CheckMate 816 and the relevance for molecular testing in that context of neoadjuvant therapy.

Dr. Stiles: Yeah. Thanks, Ryan. I think, first of all, those are incredibly important adjuvant trials. I saw 2 patients each this week on adjuvant osimertinib and adjuvant atezo [atezolizumab], so it's real-life practice. Every day, it's going to benefit patients. But I think that's easy, like you said, these are big specimens that are taken out. You've got time to decide while the patient gets better. Now, we have to shift all this even earlier because CheckMate 816 really has some pretty impressive results. We, unfortunately, don't have the paper yet. I'm told it's going to be coming out soon, but the primary endpoint pathologic complete response 24% versus 2.2%. That's with chemo-nivo versus chemo alone. Obviously, people are questioning, does pathologic complete response correlate with outcomes? Certainly, we got a signal on a press release that the event-free survival is going to be the hazard ratio is 0.63, so it sounds like it does, and I think we'll see more data on that in the next couple of months. A difference in median event-free survival of 32 months versus 21 months in the report. So everybody is excited to see this. And I think it has some advantages over the adjuvant strategy. First of all, more patients are able to tolerate it. It's just 3 cycles, and so it's not given indeterminately for a year.

And it worked across different subgroups. And we can talk about some of the nuances, but as where atezo [atezolizumab] was only looking good in the PD-L1-high. This sort of worked across different groups. The caveat to that is we don't really know what happens with these EGFR patients who are eligible and sort of, how do we then move that test? And all of a sudden, we've got to make a decision on neoadjuvant therapy. Now we need to know. It helps to know the PD-L1 maybe preoperatively, with the high PD-L1, maybe you could wait until adjuvant therapy, with the low to sort of medium PD-L1, maybe you want to give them their shot in the neoadjuvant space. But if they have an EGFR mutation, it's probably not the right thing. We don't really know the data on that and CheckMate 816 yet, but certainly, I'd be sort of hesitant to give them neoadjuvant chemoimmunotherapy. So then you have to teach surgeons all this too, and teach them to think about this and teach them to hold their horses on taking patients to the operating room while they wait for molecular testing. But that probably means we need to speed up the process somewhat either with sort of more rapid turnaround test, with consideration of liquid tests in some instances. It's just an incredibly fast-changing place that here we are speaking about a trial that hasn't even been published yet, so that tells you how fast things are happening.

Dr. Gentzler: One last question. How can the results of these tests guide therapy after surgery? Do we incorporate a full NGS [next-generation sequencing] panel at the time of surgery? And we don't have data on adjuvant therapy for ALK or ROS1, or RET. Do we factor that into how we think about adjuvant chemotherapy, adjuvant immunotherapy, do we employ targeted therapies for some of these mutations? Any thoughts on that?

Dr. Le: Ryan, I think you bring an important point in that EGFR is 1 of the 8 actionable mutations we have nowadays based on FDA and NCCN. The tumor biology between EGFR and ALK-fusion oncogenesis and potential response and benefits probably share some similarities. So we look forward to seeing trials reporting out the adjuvant setting with ALK inhibitors with ROS1. And the smaller target might require a multi-institutional or co-op group effort to really achieve the sample size for us to see. But as of now, we don't have the approval. We try to enroll patients to the oncogene trials, but I think currently we're practicing based on EGFR and PD-L1.

Dr. Stiles: Yes, and I agree. I'm excited to see what comes out of some of those trials. They're slow to grow, but we'll eventually get some readouts. I think an interesting question sometimes is PD-L1. And we had an example recently where in the pre-op biopsy, the patient had a low PD-L1, and so not particularly enthusiastic. And the question sometimes arises, do you test that whole tumor to consider them as kind of an adjuvant to atezo [atezolizumab]and then the fully resected tumor, the PD-L1 was greater than 50%. And so I would sort of sound a caution that the small biopsy sample, they're incredibly helpful for many things, incredibly helpful for moleculars. It may not always be totally representative of the PD-L1 staining.

Dr. Gentzler: And I think that's a good point. Even for molecular testing, sometimes if you have smaller biopsies, you may get a result that's negative, but it could be low levels of DNA and not sufficient to complete the full panel with high quality. So you really have to pay attention to the report and make sure that there's some confidence in the amount of DNA in some of these results.

Well, I think that's all the time we have here, so I appreciate everyone's participation, and hopefully we're able to learn a little bit about genomic testing today.

ASCO: Thank you, Dr. Gentzler, Dr. Le, Dr. Stiles, and Dr. Velcheti. Learn more about treating lung cancer at www.cancer.net/lung.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

Brielle Gregory Collins: Hi, everyone. I'm Brielle Gregory Collins, a member of the Cancer.Net content team, and I'll be your host for today's Cancer.Net podcast. Cancer.Net is the patient information website of ASCO, the American Society of Clinical Oncology. Today, we're going to be talking about clinical practice guidelines, including what they are, how they're developed, and how they can impact care for people with cancer. Our guests today are Dr. Jeffrey Meyerhardt and Dr. Scott Tagawa. Dr. Meyerhardt is the Douglas Gray Woodruff Chair in Colorectal Cancer Research, clinical director, and senior physician at the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute. He is also the Cancer.Net Associate Editor for Gastrointestinal Cancers. Thanks for joining us today, Dr. Meyerhardt.

Dr. Meyerhardt: Thanks Brielle.

Brielle Gregory Collins: Dr. Tagawa is a professor of medicine and urology and the medical director of the Genitourinary Cancer Research Program at Weill Cornell Medicine. He is also the chair of ASCO's Evidence Based Medicine Committee, which works to create clinical practice guidelines. Thanks for joining us today, Dr. Tagawa.

Dr. Tagawa: Thanks for the invitation.

Brielle Gregory Collins: Before we begin, we should mention that Dr. Meyerhardt and Dr. Tagawa do not have any relationships to disclose related to this podcast, but you can find their full disclosure statements on Cancer.Net. Now to start, Dr. Tagawa, what are clinical practice guidelines?

Dr. Tagawa: So as the name implies, there's clinical practice. So I as a practicing physician, for instance, might have a patient in front of me, and sometimes I want to know, what's the best thing to do? What is the best test that I might want to get? What is the best type of a treatment to use? I think these are especially important as the numbers of different types of cancers continues to grow, as we have more diagnostic tests and number of treatments that we have continues to grow. It's very hard for an average clinician to remember everything that's there. So we have guidelines that will give us information and general guidance for a particular situation, for a general patient population. Those don't necessarily mean that for an individual patient, that's something we have to do. But again, for the average patient in this individual situation, it helps us guide the physician or practice team in what we should do.

Brielle Gregory Collins: Got it. Thank you so much for explaining that. And, Dr. Meyerhardt, how can guidelines impact care for people with cancer?

Dr. Meyerhardt: Yes. So there's a lot of data that's out there for a lot of different cancers. And so to keep track of that, all of the different pieces of a study, it is helpful for groups of experts to get together and say what's really the right care for patients with this condition and what are the different options for them. And it really helps to really collate those all together and to be able to help clinicians decide what's the right initial step and subsequent steps for the care of a patient. As Dr. Tagawa said, it may not be the exact thing that's right for every patient. And the guidelines really do help with some of those caveats, like if the patient has certain liver function or if the patient has a certain molecular marker or something about their tumor that makes their cancer a little different, what would be the way to treat that as well? So guidelines really do help clinicians guide what's the right care for a patient at different steps along their cancer course.

Brielle Gregory Collins: Okay, thank you. And Dr. Tagawa, I want to talk a little bit about how guidelines are created. So can you describe the overall guideline development process?

Dr. Tagawa: Sure, there's a number of steps. So 1 step is identifying which guidelines are needed. So when there is a need. For instance, when there is more than 1 type of a treatment available and some data, then we generally consider that 1 of the most important types of topics to cover. When there 100% agreement with everyone in the world that 1 thing should always happen, that's less important for guidelines. And when there's zero data, that's also less important for guidelines. Although there are different types of guidelines. There's evidence-based, and you've mentioned the name of the committee that I'm on right now, Evidence-Based Medicine. But there can be consensus. So getting a group of different stakeholders, meaning physicians, nurses, etc., plus patients, together to come up with a consensus or expert opinion. So those do happen. But anyway, we identify a need, then we generally-- at least this is the way that we work it with ASCO, we get a panel together. At the very beginning of your statement, you mentioned conflicts. So we'll put together a panel of people with some sort of expertise, like maybe some scientific expertise or experience in treating, but also those that don't have at least too many conflicts on a research basis or financially, we will do a wide search to gather the best level of evidence, collect the evidence, and analyze the evidence into different levels.

Some types of clinical trials, for instance, are more important than others. We will synthesize that, put it all together, and then we'll come up with guidelines. Actually, 1 thing I forgot to mention in the beginning is we'll come up with specific questions. So for lung cancer of a certain type that's never been treated, what are the top questions? So that will guide the search. And then coming back, once we have all that evidence collected and synthesized and put in order, we'll then answer those questions. So 1 type of lung cancer that has a specific type of tumor genetic mutation in that setting, then we'd say treatment A is the best option, with B and C as options, for example. And that will be synthesized into a guideline and then put out to the public. Actually, there is a review process-- sorry, a public review process that anyone, at least ASCO does, that anyone in the world can have input on. And then, when we talk about peer-reviewed literature for a journal, for instance, we send it out to independent people. There are people that will review this, comment upon, that will come in, and we will revise things. And then the different guidelines hopefully are going to be approved and then published in journal formats, in internet formats, podcast format, etc., to hopefully get the message out.

Brielle Gregory Collins: Okay, thank you. I want to clarify the recommendations that are within guidelines. So basically, these panelists get together and they review the necessary evidence to make the recommendations. Is that correct?

Dr. Tagawa: Correct. And there are different levels of evidence and different levels or strengths of recommendations. So when there's a lot of high-quality evidence, and it all points in the same direction, that is going to be a very strong recommendation with a high level of evidence. And then there's intermediate, and then there's less evidence or extrapolated evidence, in which case, there still might be a recommendation because some of the time, let's say, for instance, in a rare tumor type or a common tumor type that has a manifestation, say the cancer that spread to the brain, called brain metastasis, that hasn't been studied before, but we want to know what to do if we get into that situation. So sometimes there are statements that will say in this situation with the best available evidence, our panel recommends this.

Brielle Gregory Collins: Okay. That makes sense. And Dr. Meyerhardt, I want to talk a little bit about the role of clinical trials in guideline development. So can you talk a little bit about that role that clinical trials play in the development process?

Dr. Meyerhardt: Yeah, I think particularly for treatment for patients, a clinical trial is really critical. So a clinical trial is basically asking a question about a treatment. Sometimes it may be that everyone gets the exact same treatment. Sometimes it's just trying to find initially a dose of a treatment. And then ultimately trials often will be randomized to either something that's standard treatment or comparing 2 different treatments to see which has more efficacy and safety and considering quality of life and other factors that are important in the treatment of patients. And as Dr. Tagawa said, the level of evidence is important in considering guidelines. And so when a guideline is being created, we do look at trials that are particularly randomized trials, trials that have larger populations, trials that may have a more diverse population, so we can understand how certain treatments may be different based on various demographic factors of the participants in that trial.

And they really are critical because you could do a trial of 10 or 20 patients, which occasionally is enough to enter a trial depending on the condition. But for the most part, there could be some just randomness to the results where it's not as clear that it's as effective as we hoped if we did it in a much larger population. So really understanding how the trial was conducted, and for the most part, clinical trials will be presented in a meeting and eventually published in the literature where there are experts in that field who would then review the manuscript, the paper related to it, and really can kind of dissect how was the trial done and the importance of the trial and critically make sure that the results that are out there that are then used by guidelines really do reflect, hopefully, what the drug is doing for patients and how they're tolerating it and other factors.

Brielle Gregory Collins: Okay, so let's say a guideline publishes, and then new research comes out. What happens at that point?

Dr. Meyerhardt: Yeah. And there's different guidelines that are used by clinicians. So ASCO, the American Society of Clinical Oncology, puts out guidelines that are a very comprehensive review of the literature and provide all that sort of data from the literature that was reviewed. There are other groups that put out guidelines more in a little bit of a table format. And how new research gets fit in is different depending on the organization. So, for example, with ASCO, there's occasionally situations where there's already a guideline that something will change and they have different mechanisms. They have the provisional clinical opinion mechanism. So a way to sort of quickly put out something that really will change the standard and really needs to be considered as a change. There are trials ongoing constantly. And if there are things that really should be considered for patients sooner than some set time period, there's ways to help incorporate those results, and how do we think about using it for our patients?

Brielle Gregory Collins: And Dr. Tagawa, what changes or advances do you see developing in clinical practice guidelines?

Dr. Tagawa: I think that we want to retain the type of guideline that is evidence-based and will in a way, every time a change is going to be made, still start from scratch and make sure nothing is missed and be comprehensive. But at the same time, being nimble and be able to make changes, sometimes in real-time. Fortunately for physicians that treat cancer as well as our patients and their families, we're making new advances all the time. So hopefully we can match those with the evidence and produce guidelines. But then also on the user end, I'll call the user the average oncologist who may just want to make sure they're doing the right thing or sometimes is not sure what to do, to have it in a format that's very easy, sitting in the clinic about to see a patient or seeing the patients saying, "What should I do?" To have that readily available, for instance, at form.

And then even better for some of us that spend a lot—I think some of you might go to your doctor and he or she is typing on a computer. We're trying to keep up. If the guidelines are melted into what's called an electronic medical record, we just put in the diagnosis and the stage and what the patient has received before. That might pop up to, number 1, help the doctor in that situation, but also help prove that that doctor is providing what's called evidence-based medicine. So maintain the evidence base, but have it as user-friendly as possible is at least one of the goals over the next several years, hopefully.

Brielle Gregory Collins: Very nice. Thank you both so much for your time and for sharing your expertise today, Dr. Meyerhardt and Dr. Tagawa.

Dr. Tagawa: It's a pleasure.

Dr. Meyerhardt: Thank you so much.

Brielle Gregory Collins: And if you're interested in learning more about ASCO guidelines, Cancer.Net is a great place to go to find patient-friendly summaries of those guidelines.

ASCO: If this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

Brielle Gregory Collins: Hi, everyone. I'm Brielle Gregory Collins, a member of the Cancer.Net content team, and I'll be your host for today's Cancer.Net podcast. Cancer.Net is the patient information website of ASCO, the American Society of Clinical Oncology. Today we're going to be talking about the psychosocial challenges unique to survivors of gynecologic cancers and how survivorship care plans can be helpful to survivors of these cancers. Our guests today are Dr. Fay Hlubocky and Dr. Merry Jennifer Markham. Dr. Hlubocky is a licensed clinical health psychologist with an expertise in psychosocial oncology and a health care ethicist at the University of Chicago in Chicago, Illinois. She is also the Cancer.Net Associate Editor for Psychosocial Oncology. Thanks for joining us today, Dr. Hlubocky.

Dr. Hlubocky: It's an honor and a pleasure to be here with all of you today. Thank you so much.

Brielle Gregory Collins: Dr. Markham is Chief of the Division of Hematology and Oncology and a clinical professor in the Department of Medicine at the University of Florida in Gainesville, Florida. She is also the Cancer.Net Associate Editor for Gynecologic Cancers. Thanks for joining us today, Dr. Markham.

Dr. Markham: Thanks so much for having me. This is going to be fun.

Brielle Gregory Collins: Absolutely. Before we begin, we should mention that Dr. Hlubocky and Dr. Markham do not have any relationships to disclose related to this podcast, but you can find their full disclosure statements on Cancer.Net. Now to start, Dr. Hlubocky, what can survivors of gynecologic cancers expect during the transition from treatment to survivorship?

Dr. Hlubocky: It's such a very important question. So this stage of survivorship, and if we think about the cancer survivor as anyone with the time of diagnosis, but especially when your treatment ends and that kind of later stage of survivorship begins, both anecdotal reports by survivors as well as research tells us this is very much a time of ambiguity. So complicated feelings such as depression and anxiety can still arise. But there's also this change in one's life and daily activities. So from the constant monitoring and treatment that the survivor actually had to go through and be engaged in constant contact with the team, now it's a time of sometimes emptiness. Patients have told us about not really knowing what to do, missing that contact, that monitoring. And so that can certainly leave us with a lot of complicated emotional distress. But also paradoxically, there are these feelings of greater purpose and feeling and meaning leading to post-traumatic growth. Might not be immediate. As soon as, of course, the treatment ends, there can be some difficulties, even with relationships and social relationships, and we can talk about some of the psychosocial challenges, but that's what at least has been reported both anecdotally also from a research perspective.

Dr. Markham: I think that that's exactly right. I think what I see in the clinical side of the patient care is exactly that. I think a lot of people who just finished their cancer treatment don't quite know what to do with themselves. They've just been sort of released back to their lives, hopefully returning back to somewhat of a normal or a new normal life. And it's definitely an anxiety-provoking period of time. And I tend to see in the clinic room a lot of fear of what's going to happen next and what should I be doing and what should I be looking for? And also on the flip side, I think you mentioned relationships. A lot of people who I see in the exam room are telling me when they're done with treatment, I'm still having these feelings. I'm still recovering from some of my treatment experience, but my family or these friends are expecting me to just get on with life. And I'm not quite sure I know how to do that yet.

Brielle Gregory Collins: Thank you both for your perspective on this. And Dr. Markham, one of the tools someone might use during this transition is a Survivorship Care Plan. So can you please explain what a Survivorship Care Plan is?

Dr. Markham: A Survivorship Care Plan is traditionally a document, some type of a physical document or an electronic document that describes the treatment that the person has been through, describes who the physicians were involved in their care, can be very in depth, can include things like the specifics of the pathology, diagnosis, and the stage. It can also include and should include some things to look out for and what the follow up will be moving forward in the future. I think of it as really a guide and a document to refer back to so that person who receives it knows exactly what they were treated with, they know the dates of their treatment, they know who their doctors were, they know what their diagnosis and stage was. And they have a plan moving forward that they can use for their own empowerment and engagement with the health system, but also their other doctors that can utilize this as well to help know best how to monitor that patient.

Brielle Gregory Collins: Absolutely. And why do you think Survivorship Care Plans are especially important for survivors of gynecologic cancers?

Dr. Markham: I think they're important really for lots of patients, lots of people who have various cancer diagnoses. Cancer treatment for gynecologic cancers tends to be multidisciplinary, meaning that they may see a gynecologist, they may see a gynecologic oncologist, which is a surgeon who specializes in gynecologic cancers. They may also see a radiation oncologist and a medical oncologist and a genetic counselor and a psycho-oncologist. So there's so many parts to that treatment course that it can be very overwhelming. And I think for any patient who goes through such a complicated experience, not just treatment, but the whole diagnosis piece through treatment, really can benefit from having just a quick and easy reference. A summary. We also found these to be very important in times of natural disasters, for example. So someone who has lived in a hurricane zone or even in the beginning of the pandemic, it's nice to have all of your information in one easy-to-access PDF or Word document or even electronically in your email. This is really helpful for transitions and care.

Brielle Gregory Collins: Thank you so much. Yes, it definitely seems like it's a critical part of that survivorship aspect. And Dr. Hlubocky, I know you touched a little bit on the psychosocial challenges that survivors might face, but can you tell us a little bit more about some of these challenges that are unique to survivors of gynecologic cancers?

Dr. Hlubocky: Yeah. So certainly one's emotional well-being and physical well-being can be impacted. So we talked a little bit about depression and anxiety, and also sometimes folks have reported post-traumatic stress symptoms. But again, everyone's individual, everyone can vary when it comes to the mental health state. We know a recent study was conducted in Utah just last year that said, specifically, ovarian cancer patients are at a little bit more heightened risk of anxiety and depressive disorders in that longer kind of ovarian cancer survivorship phase. So that's really important for us to know. Certainly also uterine survivors as well. We have to be very conscious when it comes to mental health constraints, but there's also some physical well-being or quality of life, well-being constraints, sleep can be impacted, sleep and insomnia, pain and fatigue. We know that patients record a significant amount of fatigue as well. And that really does take time. And there are certain things, for example, exercise. But additional challenges will be with sexual health, sexual libido. We know that that changes. An altered state of self-image. Certainly, we know that cancer can impact one's self-image of who that woman is. And that as well as financial concerns might be another issue.

Dr. Markham talked about the change with family relationships and friends. They may expect you to be that person that you were before the cancer. And we know and a lot of patients have told us that it's a new normal phase for me, right? A new normal. And if we think about the cancer as being a traumatic experience, we certainly know that patients are forever changed, and it isn't necessarily for the negative. Again, there can be a lot of post-traumatic growth, a lot of resilience. And that, again, isn't necessarily going to be immediate. But certainly talking to survivors in that longer phase, we know that a lot of post-traumatic growth, a lot of meaning, a lot of purposes, a lot of impact on spiritual well-being, but it doesn't mean that one is free from stress.

Brielle Gregory Collins: And do you mind just discussing how survivors can cope with some of these challenges?

Dr. Hlubocky: Absolutely. There are a number of evidence-based treatments. For example, especially psychosocial, and then mental health treatments such as cognitive behavioral therapy, mindfulness-based reduction, using techniques like journaling, using meditation, things like this. And your psychosocial support team, if you don't have it in your cancer center, we certainly have cancer community support programs within each city. These are free community support programs where they can actually help to provide psychosocial support, either in individual or group settings. So there's lots of different modalities that could be used. Adopting breathing techniques, for example, to help address anxiety. These are the folks that can really help you teach you how to adopt some of these practices in that. So certainly there's peer support. We know peer support is a wonderful tool. At my institution, we have a peer support program. And it's really just helped both that longer-term survivor give back to a certain extent. They felt like they've gained so much being a patient and learning from that experience that they very much wanted to mentor active patients. So certainly, we know peer support, social support is very important. Individual therapy, group therapy, and that.

So don't hesitate to reach out to your psychosocial support team if it's in the cancer center. If not, talk to your oncologist or your oncology team and try to identify what are the resources within. We understand that sometimes patients don't want to come back to the hospital, and that's completely fine. We want you to get back to your life. But recognizing the fact that being a survivor is also part of this new life. So we're here to support. And empowerment is key and also recognizing that your lifestyle really focusing on exercise and nutrition and sleep is vitally important also in this new phase. But recognizing as well that we have to be cautious, that this will take time for you to adopt certain lifestyle strategies. So start with the little bits. Just even going for a daily walk if you're able to. Just daily walk around the house, so to speak. Those are the little things. And assigning yourself homework to do something just to get out of the house, so to speak. But recognizing that this will take time.

Brielle Gregory Collins: Yes. Thank you, Dr. Hlubocky. And you mentioned this term, cognitive behavioral therapy, as one of the methods for coping. Can you just describe for listeners what cognitive behavioral therapy is?

Dr. Hlubocky: Oh, sure. It's a specific type of psychotherapy where we actually target what we call automatic thoughts that can be associated, for example, with either depression or anxiety or some other mental health conditions. And we look at their core beliefs. Sometimes some thinking can be black or white. It'll never get better. Well, we know that's not necessarily the case. Maybe for that moment, it doesn't feel like it won't get better. So therapists such as myself that are trained in this modality can actually help you to identify these automatic and core beliefs and help you change them or modify them or what we call reframe them. So that's very therapeutic when it comes to healing. As well as we know, sometimes the cognitive piece can be really tough for folks. So behaviorally, it's just changing one's behavior, so to speak. So as I mentioned, exercise. Sometimes it's really easier to get people moving than it is to change one's thoughts. So prescribing exercise daily or prescriptions for social support, going out and meeting with people, these are the things that can help patients down the line, certainly in the survivorship space. And we know that folks need that. And cognitive behavioral therapy can be both done in an individual level as well as there are certain groups that can be done as well in a group setting. So everyone's different. What is your preference? You can't go wrong no matter what. It's all about empowering yourself. It's all about rewarding yourself for what you've gone through. And right now, your lifestyle is the most important thing. So you have to be a priority.

Brielle Gregory Collins: Absolutely. Thank you so much for explaining that. And Dr. Markham, are there any other survivorship challenges or any other methods of coping you want to add?

Dr. Markham: Well, it's a very complicated time and there is not one particular issue that faces each of these patients or women with gynecologic cancers. I think that the psychosocial piece is very important. And what is most important I think from my mind for the listeners is that there's a discussion about, what should I expect? And I think that question to the oncology team is really an important one. What should I expect moving forward? What should I be on the lookout for? And are there things that I can do that will help me on that path?

Brielle Gregory Collins: Absolutely. And going back to Survivorship Care Plans and using them as a tool during this transition, where can survivors go to find Survivorship Care Plans specifically for gynecologic cancers?

Dr. Markham: So amazingly, Cancer.Net has a fantastic resource available with Survivorship Care Plans. And they are very similar for various cancers. But there are some that are directly focused for women with gynecologic cancers through Cancer.Net. And it's very easy to search. You can type in "Survivorship Care Plan" into the search bar and the page will come up with these. A person can print this or can share it with their oncologist. And the cancer care team may actually be presenting this to the patient already. So there's a variety of resources really. But for someone who is interested in just taking a glance at what they may look like, there's a great template available on Cancer.Net.

Brielle Gregory Collins: Thank you so much. And thank you both for your time and for sharing your expertise today. It was so great having you both.

Dr. Markham: Thank you so much for inviting us. This was great.

Dr. Hlubocky: Absolutely. Thank you. And thanks to all the Cancer.Net listeners. We're here to help.

ASCO: If this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

[music]

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, Dr. Kedar Kirtane discusses new research from the 2022 Multidisciplinary Head and Neck Cancers Symposium, held February 24-26 in Phoenix, Arizona, including research on disparities in head and neck cancer, treatment for HPV-positive oropharyngeal cancer, and strategies for reducing side effects from treatment while still keeping high effectiveness.

Dr. Kirtane is an assistant member and medical oncologist at Moffitt Cancer Center in Tampa, Florida, with a focused interest in the treatment of head, neck, and endocrine malignancies. He is also the 2022 Cancer.Net Specialty Editor for Head and Neck Cancers. View Dr. Kirtane's disclosures at Cancer.Net.

Dr. Kirtane: My name is Kedar Kirtane. I am an assistant member at Moffitt Cancer Center in Tampa, Florida. And today, I'm going to discuss some of the highlights from the recent 2022 Multidisciplinary Head and Neck Cancers Symposium held in late February in Phoenix, Arizona. For many of us, it was the first in-person meeting being attended in the last few years due to the pandemic. The talks were truly fantastic, and above all, it was nice to see colleagues, friends, and collaborators from all over. There is no way I can go over every incredible talk that was presented, but I wanted to highlight a few of the talks that I found most compelling and interesting.

So the first was the first keynote discussions by Dr. Sharon Spencer at the University of Alabama at Birmingham and Dr. Charles Moore at Emory University. They had a wonderful discussion on cancer disparities and head and neck cancers. It is unfortunately very well documented that African Americans with head and neck cancer have worse outcomes. They discussed efforts made in both Alabama and Georgia to help combat disparities in head and neck cancer outcomes for African Americans. Dr. Moore described the evolution of his interest in tackling disparities in his local communities in the Atlanta Metropolitan area, where he first held cancer screenings out of the back of his car and seeing firsthand the poverty and lack of infrastructure that contributes to the daily disparities he encounters in his clinic.

Both speakers discussed that it is imperative to increase representation of underrepresented communities into head and neck cancer clinical trials to ensure generalizability of results. And though this is very certainly easier said than done, as both speakers acknowledged, this is still an interesting aspect of clinical care that many of us encounter, where it is difficult for a variety of reasons to increase the representation of diverse communities under clinical trials. And I think this is one strong way of really doubling down and trying to combat disparities and outcomes, but I think a lot more is needed. In addition to increasing clinical trial participation, there are ways to combat implicit biases, improve local infrastructures to provide care, and engage key stakeholders for standard of care in clinical trials to minimize racial and ethnic bias. So both of these talks were really wonderful and talked about all of these things and how to incorporate them into your daily practice. As advances in the cancer world grow at exponential rates, it's really important that people from all walks of life are involved, and Doctors Spencer and Moore are doing wonderful work in their local communities and beyond to make sure this happens.

The second topic I wanted to discuss today comes from my own institution, Moffitt Cancer Center, and my colleague, Dr. Michelle Echevarria. I was not directly involved with this study, but I am obviously a colleague of Dr. Echevarria, and this study was done at my center at Moffitt. So she discussed the study that she conducted on the kinetics of circulating human papillomavirus DNA, or HPV DNA, in plasma and oral gargles from patients with HPV-positive oropharynx cancers that are treated with definitive radiation therapy. HPV, or human papillomavirus, is a sexually transmitted virus that can cause cancer. It is the same virus that causes the majority of cervical cancer, and it is actually now believed that in America, this represents the major cause for oropharynx cancers. This is in direct contrast to 20, 30 years ago where HPV as a cause for oropharynx cancers was not even known, and most of the disease was thought to be related to tobacco or alcohol. Now, there are ways to check for circulating HPV DNA in the bloodstream and also in oral gargles for patients with HPV-related head and neck cancers. This is by no means considered a standard of care, but the goal from many institutions is to try to figure out how to incorporate these blood tests in sorting out how to treat patients and potentially how to detect for recurrence. So by noninvasively being able to measure this DNA in the bloodstream, this offers potential opportunities to personalize radiation dose, i.e. for people whose HPV DNA does not go to zero initially after treatment, and also as a potential biomarker for recurrent disease.

Dr. Echevarria and her team analyzed circulating HPV in blood and in oral gargle samples from patients enrolled on a clinical trial of radiation alone for the treatment of HPV-related oropharynx cancer. And in this study, plasma and oral gargles were collected prior to the initiation of treatment. So they had a baseline HPV level in their oral gargle and/or their plasma. And they also checked it during week 4 of treatment, at the end of treatment, and then at 2 to 3 months after treatment. That latter endpoint is a clinically relevant one because many times, this is when providers are getting imaging and checking to see if the treatment that was given to the patient actually worked. And what this study found, briefly, was that a clearance of plasma HPV levels was associated with a reduction in cancer size as seen on CT imaging. And this suggests that there are future avenues for research where potentially one could study a subset of patients who immediately clear the HPV in their bloodstream early and then potentially de-escalate those therapies. So really, the question is whether those patients need the full gamut of radiation or whether they can safely avoid toxicity and at the same time maintain those high cure rates. So this was a really interesting study, and I think these sorts of studies checking for HPV in the bloodstream are going to become more and more prolific as we figure out how to incorporate this into standard of care and whether it actually ends up changing clinical practice.

Speaking of HPV and de-escalation, there was certainly a lot of discussion regarding de-escalation of therapies. Now for people who don't know what that means, what that means is that, as I mentioned earlier, HPV is a known cause of oropharynx cancers in America and abroad. And what we know now is that HPV-related head and neck cancers actually just have a better prognosis, a better cure rate, a better survival rate compared to cancers of the head and neck that are related to tobacco or alcohol. So really, the question has come up as to whether the treatment paradigm that we have, which is 6, 7 weeks of radiation, sometimes adding chemotherapy, do we really need to throw the proverbial kitchen sink at treating these patients when they already do so well?

Dr. Chera from University of North Carolina and Dr. Hayes from University of Tennessee discussed radiation and chemotherapy, respectively, in de-escalation strategies. I will say that Dr. Hayes said something really thoughtful, which is that the greatest toxicity is treatment failure, so there has to be clinical equipoise in how we choose the patients that we are safely deeming to de-escalate therapy. The last thing we want to do is decrease toxicity in the short term for patients if we don't at the same time maintain those high cure rates that are seen in HPV-related cancer patients. Dr. Chera discussed a variety of studies regarding reduced radiation dose, either after primary surgical management of head and neck cancers or as part of definitive therapy. And he conceded that while some of his treatments for his patients have changed as a result of phase 2 studies, that he acknowledged that there was a need for larger phase 3 studies to really definitively conclude that de-escalation of radiation dose is okay to do. Dr. Hayes discussed a variety of clinical trials that have been done with different chemotherapy regimens. Now the standard of care that we use is something called cisplatin. And while most of the randomized control trials have shown inferiority of non-cisplatin-based chemotherapy regimens, there's still a large future out there to figure out which subset of patients could safely either avoid chemotherapy, get a chemotherapy that is perhaps less toxic, or give a chemotherapy just with less dose. And while none of these have become yet standard of care, obviously, just like I mentioned earlier with checking HPV in the bloodstream, this is going to be a really significant part of the clinical trial landscape moving forward over the next 5 or 10 years.

So, in summary, this was a really great conference, one that focused on disparities, one that focused on HPV-circulating tumor DNA in the bloodstream and also de-escalation strategies for HPV head and neck cancer patients. So thank you for listening to this brief summary of new research in head and neck cancers.

ASCO: Thank you, Dr. Kirtane. You can find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

Greg Guthrie: Hi, everyone. I'm Greg Guthrie, and I'm a member of the Cancer.Net content team, and I'll be your host for today's Cancer.Net podcast. Cancer.Net is the patient information website of ASCO, the American Society of Clinical Oncology. Today, we're going to be talking about the ASCO provisional clinical opinion, "Somatic Genomic Testing in Patients With Metastatic or Advanced Cancer." Our guests today are the co-chairs of the team that wrote these recommendations. Dr. Funda Meric-Bernstam from the University of Texas MD Anderson Cancer Center in Houston, Texas. Thank you for joining us today, Dr. Meric-Bernstam.

Dr. Meric-Bernstam: Thank you for having us.

Greg Guthrie: And our second guest today is Dr. Mark Robson from Memorial Sloan Kettering Cancer Center in New York City. Dr. Robson, thank you for joining us today, too.

Dr. Robson: Thank you for having me.

Greg Guthrie: So before we begin, I should mention that Dr. Meric-Bernstam does not have any relationships to disclose related to this podcast. Dr. Robson has led clinical trials in PARP inhibitors but has not received any personal compensation for this research. Full disclosures for this podcast can be found on Cancer.Net. So, Dr. Robson, let's begin by discussing what a provisional clinical opinion is and why they are important.

Dr. Robson: So there are times when there are sea changes or incredibly important changes taking place in oncology practice. And sometimes these are clinical trial data, and sometimes they are more global. And this is a situation where it's one of those global challenges. And what ASCO does in situations like this is pull together a group of experts to provide guidance for the membership through a process of discussion and informal consensus rather than necessarily direct evaluation of clinical studies. And this is important because it allows the membership to benefit from these expert opinions.

Greg Guthrie: Now, Dr. Meric-Bernstam, this provisional clinical opinion discusses somatic genomic testing in metastatic or advanced cancer. What is somatic genetic testing, and how is it used in cancer treatment?

Dr. Meric-Bernstam: Oh, thank you. This is a really exciting time in the last decade. We have a lot more tools to understand cancer biology. And cancer is a genomically-driven phenomena, where there's alterations in the DNA, in the tumor, that confers the cancer cells a competitive growth and survival advantage. And only 10 years ago, we had the capability of doing this 1 gene at a time, to sequence a gene to see what is different, but now we have technologies where we can look at several hundred genes at a time. We are referring to these as multigene panels. And we're talking about genomic testing or somatic genomic testing. These are tests that look at several hundred genes, either looking at the tumor sequence alone or looking at the tumor sequence and comparing it to the normal sequence so we can see what has differed in the tumor that may give it a competitive advantage. We're doing this to be able to identify if there are genes that are altered that are therapeutically actionable. What we mean by that is, is there an alteration that we think confers the cancer cell an advantage for which we have a drug that either directly or indirectly we can use to help inhibit the cancer cell growth or preferably cause the cancer cell death?

Greg Guthrie: Great. And so how is somatic testing different from germline testing?

Dr. Robson: So somatic testing is testing the DNA or the nucleic acids, if you will, in the tumor itself, and germline testing is testing the DNA in normal tissue. And so the DNA in the normal tissue is what people are born with, and of course, most of the DNA in the tumor is the same as what people were born with. But there are specific changes that develop as the cancer arises, and it's those specific changes that are called somatic alterations.

Dr. Meric-Bernstam: This is actually a really interesting point though because some tests report out germline alterations as well because only the tumor is sequenced, while some tests report the tumor, only subtracting what was in the germline. Thus, unless the germline result is specifically reported, a patient that has a known germline alteration may be surprised to see that it's not in the tumor report. And on the flip side, a tumor-only test may find a germline alteration, and thus it's important that physicians and patients are aware of that. That needs to be further pursued with the genetic testing.

Greg Guthrie: Wow, just a wealth of information coming from this testing now. Sometimes I hear the term next-generation sequencing mentioned in regard to cancer. Does this provisional clinical opinion also touch on that?

Dr. Meric-Bernstam: Yes. When we are referring to genomic testing panels or multigene panels, we are talking about the next-generation sequencing technology that has the ability now to use a small amount of tumor to be able to report out the sequence of several hundred genes. We have, of course, broader panels also coming, such as whole exome sequencing, whole genomic sequencing. Although, majority of our provisional clinical opinion is talking about the use of these in several hundred gene panels.

Greg Guthrie: Amazing. Alright. Dr. Meric-Bernstam, so what should people with cancer and their loved ones know about this opinion?

Dr. Meric-Bernstam: This has been a really complicated time because the introduction of next-generation sequencing made genomic testing available, but to be fair, not widely available initially. Only more recently is it more broadly available, and there's been some confusion about which patients with which diseases should get or can get genomic testing or would benefit from genomic testing. So we wanted to frame this by first highlighting that if a patient has a metastatic or advanced cellular tumor type and there is a genomic biomarker that is linked to a therapy approved for a regulatory agency, or they have a tumor type where there's a drug that's approved but there's a known genomic resistance marker, these are scenarios where we feel patients should get genomic testing. Now, the more complicated area, a little more controversial, has been scenarios where the patient has a disease that is not one of those diseases that has a disease-specific approval for a drug. And in that scenario, we believe there's still value in genomic testing for several reasons.

There's been several new drug approvals for what we call tumor-agnostic drugs. That means if you have an alteration that gives you sensitivity to immunotherapy because you have what we call microsatellite instability, and some next-generation sequencing panels can report that out, then, regardless of your tumor type, you may be able to get offered immunotherapy. If you have multiple mutations in your tumor, something we call the increased tumor mutation burden, that is now linked to immunotherapy approval. So irrespective of tumor type, if a patient is eligible for immunotherapy, they benefit from getting genomic testing. And then on top of that, we now are seeing more and more that patients may have a genomic alteration that we think is a compelling target. But they may have it-- they may have it in a disease where that drug was not approved. And we're now starting to see that in many clinical trials. We're seeing activity by targeting those alterations. So there may be additional opportunities, especially for clinical trial enrollment, by identifying these potentially actionable alterations in other diseases.

So taking this together, we believe multigene testing will provide both additional approved indications and clinical trial indications. And in addition, fusion testing can identify TRK fusions, a fusion type that's found commonly in some uncommon cancers and uncommonly in some common cancers. But when it's found, it is a very compelling target. So again, because patients would be eligible for TRK inhibitors, irrespective of their tumor type, that's another scenario where next-generation sequencing may be beneficial for patients with advanced and metastatic disease, irrespective of tumor type.

Greg Guthrie: Wow, that's just an amazing overview right there. And one question that occurs to me is, is all of this genetic testing done from a biopsy sample? Or are there other ways a patient may experience this testing?

Dr. Meric-Bernstam: The traditional tumor-based testing is usually done either from a surgical sample or a biopsy sample. And again, it could be tumor-only testing or tumor plus a normal. Usually, normal would be something like blood as a comparator. However, there are times where a patient doesn't have a tumor accessible for a biopsy. In that scenario, there is now the opportunity to look at circulating free DNA to do panel testing on circulating free DNA for some of the more common actionable alterations. So there's a lot of momentum in using that approach, and this is what we often refer to as a liquid biopsy. And the liquid biopsy strategy is also very interesting because it's another way to pick up what changes of the tumor with treatment as well. So there's a lot of research going into using liquid biopsies when the patient also progresses on targeted therapy to see what has changed and how we need to change our therapy to address the tumor's evolution.

Greg Guthrie: Wow. Thanks for that, Dr. Meric-Bernstam. Dr. Robson, what are the emerging ways that genetic testing may be used to help people with cancer?

Dr. Robson: I think there are many, many ways. I was reflecting on this question, and I think it's important to kind of separate, as we did earlier, what we mean by genetic testing, again, because I think there's a lot of confusion. And there's certainly a lot of work going on in terms of testing of inherited DNA, so germline testing, to identify risks for cancer and potentially therapeutic targets. And that's not something that was discussed in this particular opinion, but it is an important way that genetics is being used to help people. On the side of the folks who already have cancer, the application of genetic technologies, as Dr. Meric-Bernstam said earlier, is identifying more and more targets. In other words, more and more alterations that are driving the cancers and for which we can test new drugs and hopefully achieve successes in a much more focused and less toxic way. And that work is going on at an exponential pace, and indeed, perhaps most of the new drugs that are entering the development pathway right now are indeed targeted therapies, not conventional broad-spectrum chemotherapies.

The genetic technologies are also being used as, again, Dr. Meric-Bernstam said, to look at DNA from the tumors that are circulating in the bloodstream. And one way is the liquid biopsy, which is for characterization. But another way that's coming online is just simply to look for the presence or absence of circulating DNA in people who are, for instance, post-op and don't have any evidence of disease to see whether or not they might, in fact, have some cancer that hasn't been detected by imaging. And then the hope is that we could then intervene earlier in that setting and perhaps prevent those circulating DNA from representing true metastasis, detectable metastasis. And again, a lot of work going on there. And there's a diagnostic and prognostic component to what's happening as well. There are, unfortunately, a number of people who present with metastatic cancer, and it's not obvious at all where that started. And work is being done now to use testing of the tumor DNA to help categorize the tumors, to direct the correct therapies, instead of just doing something generic and empiric. And there are many, many other ways that genetic technologies are being applied. It's really 1 of the 2 big frontiers in cancer therapy right now. The other one, of course, being immunotherapy. But it is an exciting time, and I think it's just going to continue to grow as the technologies become more and more innovative.

Greg Guthrie: That's really exciting. And thank you for sharing all of that perspective. I really wonder if helping with this somatic testing can help increase enrollment in clinical trials, too, to advance progress in other rare cancers?

Dr. Robson: I think it did, not necessarily just in rare cancers. I mean, people are—

Greg Guthrie: Agreed.

Dr. Robson: —certainly doing testing in common diseases and identifying these new targets. And you're exactly right. The only way we're going to be able to develop new therapies in that setting is through clinical trials. And so, for the appropriate people, genetic testing or testing of the tumor or somatic testing could very well identify clinical trial opportunities for them, and that's the way we're going to move forward.

Greg Guthrie: Outstanding. And again, I really love this distinction between somatic and germline testing and clarifying that for our listeners today. Dr. Meric-Bernstam and Dr. Robson, thanks so much for your time today and for sharing your expertise on these ASCO recommendations. It's been great having you and chatting with you today.

Dr. Robson: Thanks.

Dr. Meric-Bernstam: Thank you for having us.

Greg Guthrie: And for our listeners, if you'd like to learn more about genetics, genetic testing, and cancer, visit www.cancer.net/genetics. Thanks so much for joining us today, and be well.

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