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 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. 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 the 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 genetic conditions linked to kidney cancer and what people with these conditions should know about genetic counseling. Our guests are Dr. Brian Shuch and Lauren Bear. Dr. Brian Shuch is the director of the Kidney Cancer Program at UCLA Health in Los Angeles, California. He is also 1 of the specialty editors for genitourinary cancers at Cancer.Net. Thanks for joining us today, Dr. Shuch.

Dr. Brian Shuch: Great. Thanks for having me.

Brielle Gregory Collins: Also joining us is Lauren Bear. Lauren Bear is the lead genetic counselor at the Familial Renal Cell Carcinoma and VHL Disease Clinic at Massachusetts General Hospital in Boston, Massachusetts. Thanks for joining us today, Ms. Bear.

Lauren Bear: Thank you so much for having me.

Brielle Gregory Collins: Before we begin, we should mention that Dr. Shuch and Ms. Bear 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. Shuch, what is the definition of a genetic or inherited condition?

Dr. Brian Shuch: Really, this is any condition that would develop that is really strongly influenced by somebody's genes that they would inherit from a family member. But there are lots of kind of complex definitions we can go into, but really anything that develops directly influenced or modulated by their genes that they inherit.

Brielle Gregory Collins: Thank you for defining that. And how are genetic conditions diagnosed?

Dr. Brian Shuch: So there are different ways, obviously, with the ability to have DNA sequencing done at a fraction of the cost from 10, 20 years ago, we can quickly and effectively sequence somebody's genes. But there are some times where we see patients that they have clinical features of a particular syndrome. And we have given patients a clinical diagnosis of that condition and follow them the same way if they meet some pre-specified criteria. But not every condition actually has a clinical diagnostic criteria.

Brielle Gregory Collins: And getting into those specific conditions a little bit, briefly, what are some of the most common genetic conditions that are linked to kidney cancer?

Dr. Brian Shuch: So there are about 18 different genes, which when inherited with a damaged copy, you potentially will have some increased risk. Some of them are the well characterized ones, which everyone is familiar with that have been around for decades. Most commonly, people are familiar with Von Hippel-Lindau, which has been described now about 100 years ago, but there are other conditions too. Birt-Hogg-Dubé, which is another common 1. The 1 that I study, hereditary leiomyomatosis and renal cell, we actually believe is the most common 1 based on newer data. But other ones, such as hereditary papillary renal cell, there's a bunch of ones linked to a hereditary paraganglioma syndrome called STH. But we have plenty of new and emerging conditions, and we're learning new things every year.

Brielle Gregory Collins: Thank you for running through all of those. And if someone is diagnosed with kidney cancer, what are some of the signs that they might have 1 of these genetic conditions?

Dr. Brian Shuch: So first and foremost, when you're with a patient, you look at their age and if someone has really early age of onset, it should be a red flag. Age alone is controversial whether you should do testing, but that should be a red flag. Whether someone has 1 tumor or more than 1 tumor obviously is important. Both kidneys or 1 kidney. But taking a family pedigree is very important. Most clinicians may just say any kidney cancer, but really understanding at least 2 or 3 generations can really help kind of outline somebody's inherited risk.

Finally, the pathology. There are about 20 flavors of kidney cancer, not all of them have the same type of risk. But we actually can learn a lot from a very outstanding pathologist that looks with special immunostains or they look at particular features under the microscope. And a lot of times, a good pathologist can pick this up. And when they do, we have very high likelihood of diagnosing someone with a hereditary form of kidney cancer.

Brielle Gregory Collins: Thank you. And as far as being diagnosed and how it affects the way someone is treated, can you describe how being diagnosed with a genetic condition may change the way kidney cancer is treated?

Dr. Brian Shuch: So not all types of kidney cancer are the same. It is 1 of the most diverse forms of cancers that we have. Just because they arise from the kidney does not make them the same. There are some which are very indolent and other ones which are extremely aggressive. So if I found a patient with a 1-centimeter kidney tumor and I knew it was sporadic, I may consider watching that patient and doing what's called active surveillance. If it's a patient who actually is a family member of 1 of our patients just diagnosed with HLRCC, that patient was placed on active surveillance and there's no way we would watch that type of tumor because it has much more aggressive biological potential. We would definitely recommend intervention for someone with that type of disease. Biology of the tumor really predicts behavior.

Brielle Gregory Collins: Thank you so much. And can you describe how common it is for someone to be diagnosed with inherited kidney cancer?

Dr. Brian Shuch: So that's a great question. It's something which is not really perfectly understood at this time. There's been very wide estimates, anywhere from 1% to maybe 8% of kidney cancer might have a very strong inherited component, whether it's due to a single gene that also may be somewhat variable, but I would say it's probably less than 10% of patients actually have a strong inherited predisposition. So we don't refer all patients for testing. And everyone's threshold to send someone for testing varies. But I think obviously, talk to your clinician. I think in this era where testing is fairly cheap and the risks are very low, I think as a default, most clinicians should err on sending patients to a genetic counselor and the genetic counselor can walk things through. Often the history that a clinician takes is somewhat insufficient. And I think the genetic counselors are really great at going through a 3-generation pedigree and then deciding whether testing should be pursued. So not everyone should be referred and not everyone referred should actually undergo testing. But I think the first step usually comes with recognition by the clinician. I'm interested to hear what Lauren thinks about this as well.

Lauren Bear: Yeah, I completely agree. It's a good point that we're more than happy to meet with any patient that a physician is concerned could have a hereditary kidney cancer condition. But exactly like Dr. Shuch described, not every family history is very high risk. And so, yeah, I completely agree.

Brielle Gregory Collins: And Ms. Bear, I want to get into a little bit about genetic counseling. So if a person is referred to genetic counseling, how can they best prepare for their appointment?

Lauren Bear: So during the visit, a genetic counselor will likely ask, as Dr. Shuch described, about their personal and family history to assess risk for 1 of these conditions. And there are some helpful things that people can prepare in advance for this appointment. First are factors related to their personal history. So like Dr. Shuch described, because some of these hereditary cancer syndromes are related to specific types of kidney cancer, it may be helpful to gather information about your own cancer diagnosis and your own personal medical history if it's not already included in the referral or the medical chart, and also gathering information about your family history. So asking some people to research with their family members to see who has had any cancer, what are the ages of diagnosis in their family members' medical history. And that often, again, like Dr. Shuch described, will be to ask about children, siblings, parents, and grandparents to create that 3-generation pedigree or family tree.

I think sometimes patients like to discuss the appointment in general with their family member before it happens, because the process of genetic counseling can often involve this option of genetic testing, which could have impact on family members. So beginning that conversation early with relatives can be helpful sometimes. And lastly, some patients like to talk to their insurance carrier about coverage of the appointment itself or even about the genetic testing, although very often talking about the actual genetic testing coverage will be discussed at the appointment with the genetic counselor. So working in advance to get some of these things together can be really helpful to prepare.

Brielle Gregory Collins: Got it. And as far as the meeting itself, what happens during and after the initial meeting with the genetic counselor?

Lauren Bear: Yeah, so overall, the genetic counseling appointment will involve a genetic evaluation during the initial session and then afterwards, a discussion about any test results and/or follow-up recommendations for the patient and their family members. So during the session, as I stated before, the genetic counselor will ask about this personal and family history and ask about other features that may be suggestive of a known hereditary kidney cancer syndrome. Sometimes that might involve a physical exam with a physician, depending on the indication or the clinic set-up. The genetic counselor will provide basic understanding of genetics and the basis of hereditary kidney cancer to make sure the information that is shared and the recommendations are all put into context for the patient and their family.

And then, based on the factors seen in the personal and family history, the genetic counselor will provide a risk assessment, which is a discussion of the possible genetic risk factors that could be explaining the kidney cancer or other cancers in the family. And as, again, Dr. Shuch described, to evaluate very often, this can include a discussion about genetic testing, which can be done on blood or saliva. Both are equally accurate, and it often can be performed via a multigene panel where we look at more than 1 of these conditions at once. But it's also important to realize that this testing is optional. So it is up to the patient if they would like to proceed with any of this testing. And an informed consent is a really important part of this discussion as well, to make sure the patient understands the benefits and limitations of this testing and to confirm if they do or do not want to move forward with the testing.

So that's overall what happens during the session and afterwards, if testing is performed, then genetic testing results are communicated to the patient. Depends on the clinic set-up how that's done, if it's through a telephone call, virtual visit, in-person visit. This may be together with the physician, again, depending on the set-up. But in this results disclosure, the genetic counselors and the medical team, they're equipped to convey these results with their patients. So they keep it in context with their own personal and family history and to help the patient adjust to the results, whatever the results are, because learning about genetic test results can sometimes be challenging. So a genetic counselor's role is to provide support and help the patient adjust however they can.

Brielle Gregory Collins: So it sounds like it's really a discussion between the patient, their genetic counselor, and the rest of their health care team to see if genetic testing is something that's right for them.

Lauren Bear: That's exactly right. That's exactly right.

Brielle Gregory Collins: Got it. And how does meeting with the genetic counselor help a person with kidney cancer and their family?

Lauren Bear: So when someone first learns there's a possibility of a hereditary reason behind their kidney cancer, many questions or feelings may arise from how this could impact their own health and how it could also impact the health of their family members. And this is all very natural. So the goal, as I stated before, is for the genetic counselor to help guide the patient and their family members to learn more about their risk and figure out who else might be at risk in their family. So, for example, if a positive test result is found or a diagnosis of a hereditary kidney cancer syndrome is made, the genetic counselor's skills are to identify the appropriate follow-up for that patient. So whether it's follow up with a physician to monitor for potentially another kidney cancer, or some other type of cancer, or some other symptom related to these conditions that Dr. Shuch described. And so that's part of when we're thinking about the genetic counselor's role with the patient and their own medical care, it's for that follow-up and helping them adjust.

When we think about for their family, a genetic counselor's role would be to help identify who might be at risk. So discussing cancer risk in families is not always the top of conversation. And so the role of the genetic counselor is to help work through ways to facilitate these conversations with family members. Not everybody in the family may be interested at that moment to do genetic testing. So working with a genetic counselor can be helpful in brainstorming ways to share this information with family. Other times, family members are very eager to pursue genetic testing at that moment, so genetic counselors can help set up those consultations or find local resources. So often, long-term relationships can be established with a genetic counselor and the family and the patient.

And then also, if a negative result is obtained, there's no gene mutation detected and the patient's not diagnosed with a known hereditary kidney cancer syndrome, the medical team and genetic counselor may also still be able to provide recommendations as far as screening for the family. So it's not to say only if a positive result is found are recommendations made. So those are kind of how I think about how a genetic counselor can impact the patient and their families in a situation like this.

Brielle Gregory Collins: Thank you so much for walking through that. So for someone who is diagnosed with 1 of these genetic conditions, what are some tips that you'd share about how they can discuss the genetic condition related to their kidney cancer with their family?

Lauren Bear: Every family is very different and the genetic counselors and the physicians, their specialty is to help walk a patient through how family members might react to this kind of information and what kind of materials may be helpful to have on hand when someone wants to share this information with their family members. Many genetic counselors supply family letters detailing the results that the patient is welcome to share with their relatives, certain handouts. We've had family meetings and conference calls, which can be helpful tools. And so really the genetic counselor is really trying to help the patients have the language to facilitate these conversations or to have their own understanding. So if they can absorb this information themselves, they may be more comfortable sharing it with their relatives. And that process might take a little while to adjust to this information, to give yourself some time to ask questions of your own medical team so you can educate yourself and then feel comfortable to share it. Sometimes these discussions happen with children who may be at risk for hereditary cancer, kidney cancer syndrome. So making sure to use age-appropriate language and also having more of like an ongoing conversation rather than a one-time conversation with children can be helpful. But as with anything, as questions come up, I always say, "Don't hesitate to reach out to the genetic counselors or your medical team. We're here to help."

Brielle Gregory Collins: That's all really helpful. Thank you so much for your time and for sharing your expertise today, Dr. Shuch and Ms. Bear. It was great having you.

Lauren Bear: Thank you for having me.

Dr. Brian Shuch: Thank you.

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This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

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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 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. 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 clinical trials described here may no longer be enrolling patients, and final results are not yet available.

Before any new cancer treatment can be approved for general use, it must be studied in a clinical trial in order to prove it is safe and effective. In today's podcast, members of the Cancer.Net Editorial Board discuss 3 clinical trials that are exploring new treatment options across kidney, bladder, and prostate cancer.

This podcast will be led by Dr. Timothy Gilligan, Dr. Tian Zhang, Dr. Petros Grivas, and Dr. Neeraj Agarwal.

Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig Cancer Institute. He has no relevant relationships to disclose.

Dr. Zhang is an associate professor of medicine at Duke University School of Medicine and is a medical oncologist at Duke Cancer Institute. She has served in a consulting or advisory role for Bristol-Myers Squibb and Merck, and has received research funding from Astellas Pharma.

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. He has served in a consulting or advisory role for Bristol-Myers Squibb and Merck.

Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. He has served in a consulting or advisory role for Bristol-Myers Squibb, Merck, and Astellas Pharma.

View full disclosures for Dr. Gilligan, Dr. Zhang, Dr. Grivas, and Dr. Agarwal at Cancer.Net.

Dr. Gilligan: Hi. I'm Dr. Timothy Gilligan from the Cleveland Clinic Taussig Cancer Institute. I'm joined today by Dr. Tian Zhang from the Duke Cancer Institute, Dr. Petros Grivas from the University of Washington and Fred Hutchinson Cancer Research Center, and Dr. Neeraj Agarwal from the Huntsman Cancer Institute and University of Utah. Today, we're going to discuss 3 ongoing clinical trials in kidney, bladder, and prostate cancer.

As you may know, clinical trials are the main way that doctors are able to find better treatment for diseases like cancer. Patient participation is vital for clinical trials. By participating in the clinical trial, you can directly help researchers develop better treatment, reduce side effects, or even reduce the risk of cancer altogether.

The 3 trials we'll discuss today were chosen by members of the Cancer.Net Editorial Board Genitourinary Cancers panel from the Trials in Progress abstracts that were presented at ASCO's 2020 Annual Meeting. Because these are ongoing clinical trials, final results from these studies are not available yet. I'd like to note that none of us have any direct involvement with any of these trials. To view our full disclosures, please view the show notes for this episode on Cancer.Net.

We're going to start with Dr. Zhang discussing the trial CheckMate 914. Why don't we begin with who the study is designed for?

CheckMate 914 is a study in the adjuvant setting, so it's a study after patients have had their primary kidney cancers removed, and everybody needs to have a kidney tumor that's either 7 centimeters or larger or have extension beyond the kidney or any nodal involvement. So after their kidney tumors have been removed, this study really is in that timeframe after nephrectomy or after surgery with complete resection of their tumor.

Dr. Gilligan: What's the current standard of care for these patients if they're not on a trial like this?

Dr. Zhang: We often will compare against that standard which currently in the adjuvant setting we either do observation until disease recurrence or there is 1 oral treatment that's approved called sunitinib. But sunitinib really has some controversial data around it, and so it's not often used. And so currently, many patients are still observed as standard of care in the setting.

Dr. Gilligan: And so if a patient goes on this trial, what can they expect?

Dr. Zhang: So patients who are enrolled to CheckMate 914 are randomized to either a combination immunotherapy called ipilimumab with nivolumab, which is approved in the metastatic setting for kidney cancer, or they're placed on placebo for these 2 treatments, or there is a third cohort that receives nivolumab alone with a placebo of ipilimumab. And so these patients are receiving either active immunotherapies or a placebo, which would be our current standard of care, sort of observation until disease recurrence.

Dr. Gilligan: So patients will either get the current standard, which is observation, or else they'll have 1 drug or 2 drugs if I'm understanding correctly?

Dr. Zhang: That's right.

Dr. Gilligan: What is the hope of this study? What is the outcome that we're hoping to see?

Dr. Zhang: The primary outcome of this study is disease-free survival, so that means time until disease recurrence for all comers. And we're really trying to prolong time until disease recurrence or time until metastasis for these patients. There are some secondary outcomes that are very important as well, so prolonging overall survival as well as the incidence of adverse events that are seen from these treatments. And then there is an independent radiographic assessment to look for disease-free survival intervals as well.

Dr. Gilligan: And the hope is that these treatments will prevent recurrence or at least delay recurrence then?

Dr. Zhang: That's absolutely correct, yes. And we have had 2 other adjuvant trials with immunotherapies in this space of atezolizumab and pembrolizumab, but those trials have finished accruing. And so this is the main ongoing and accruing trial that's looking at active immunotherapy options in this space.

Dr. Gilligan: What risks should patients be aware of that they might encounter if they go on this treatment?

Dr. Zhang: So with all immunotherapies, we talk a lot about the immune mediated adverse events and just the usual rundown of those. And in my clinic, we talk a lot about the common rashes. In the GI tract, it can cause some inflammation or colitis. Very rarely, it can cause some inflammation in the lungs or liver and then very commonly, endocrine dysfunction. So we watch pituitary, thyroid, adrenal, and pancreas function very carefully. But all of these side effects are well described for the ipilimumab, nivolumab combinations as well as nivolumab on its own in the metastatic setting. So most people should know what to monitor for and what we're looking out for and how to manage these toxicities.

Dr. Gilligan: Right. So these are drugs that have been in wide use for some years now, so we have significant experience managing the side effects is what I'm hearing you say.

Dr. Zhang: That's right.

Dr. Gilligan: Is this trial still open to patients?

Dr. Zhang: Yes. This trial is still accruing. It's a global study about to enroll up to 1,600 patients. So it's a very large global trial that is still active and still accruing patients. So I would encourage people and also oncologists to refer patients for the trial at a center close to them if possible.

Dr. Gilligan: And when might we expect results for a study like this?

Dr. Zhang: These adjuvant studies take a while to finish accruing and then it takes a while to finish seeing the data. So I would hazard a guess that we're still years away from seeing the data from this trial.

Dr. Gilligan: So once again, this is for people who have had surgery to remove a kidney cancer and looking at ways to reduce the risk of subsequent relapse. Well, thank you for summarizing that so coherently and succinctly. Let's move on now, and we're going to talk about the trial KEYNOTE-992 with Dr. Grivas. Dr. Grivas, who is this study designed for?

Dr. Grivas: So this is a clinical trial, a phase III clinical trial that applies to patients who opt to pursue what we call bladder preservation, which is an attempt to keep the bladder intact and still try to treat bladder cancer with concurrent use of chemotherapy and radiation. And this bladder preservation approach applies to a proportion of patients with bladder cancer still in the bladder but not spread. And as I mentioned before, the decision to pursue that strategy depends on particular patient characteristics, how the cancer looks on the CAT scans, and also how it looks under the microscope.

Dr. Gilligan: What is the current standard of care for these patients?

Dr. Grivas: So patients who are characterized as great candidates for this bladder preservation approach, because this does not apply to everybody with bladder cancer, the standard of care right now is patients undergo what we call a transurethral bladder tumor resection, which means that the urologists go through the urethra and they resect or remove or scrape, remove the visible bladder tumor, and then the patients undergo concurrent, meaning at the same time, chemotherapy and radiation.

Dr. Gilligan: How does the study aim to improve or change the standard of care? What would be different as a result of the study if it's successful?

Dr. Grivas: So this particular clinical trial, the KEYNOTE-992, is asking the question whether the addition of immunotherapy with 1 of those immune checkpoint inhibitors that activates the immune system, does this addition add value in the combination of chemotherapy and radiation? So the patients are being randomized by a computer system to either getting chemotherapy-radiation, as is the standard of care that we just discussed, or chemotherapy plus radiation which is standard of care, plus the addition of this drug called pembrolizumab, which is an immunotherapy aiming to activate the immune system.

Dr. Gilligan: And it's given at the same time as the chemotherapy and radiation on the study?

Dr. Grivas: That is correct. It's given at the same time. And then there is also some—what we call continuation of pembrolizumab for some time after the end of chemotherapy and radiation, and pembrolizumab in this study is given every 6 weeks.

Dr. Gilligan: And what makes people think that this might be helpful to add this additional treatment?

Dr. Grivas: The notion is that the addition of immunotherapy to chemotherapy-radiation therapy has the potential to make the chemotherapy, radiation therapy work better. What happens sometimes when you give chemotherapy-radiation, this can actually result in a killing of some cancer cells and the contents of those cancer cells can be released, and they may be recognized by the immune system and stimulate the immune response. So if you combine that chemotherapy and radiation with immunotherapy with this agent that stimulates the immune system, the assumption is that this may work better compared to chemotherapy and radiation alone. But we have to do this trial to confirm whether this is true or not.

Dr. Gilligan: So patients going on the study, basically, either they'll get the standard of care, which is the chemotherapy and radiation, or the standard of care plus the addition of immunotherapy to see if that results in better outcomes. Am I understanding that correctly?

Dr. Grivas: That's exactly right. And the outcomes are being measured by how many patients maintain the bladder intact, in place without the need to remove it, without the need for cystectomy. And also, at the same time, we want to see if those patients can maintain a cancer-free status, so whether the treatment results in a cancer-free state and whether we are measuring a recurrence as Dr. Zhang mentioned before, if the cancer comes back. And also, of course, we measure how many patients are alive over time. So the goal is to see if we can improve upon the rate of patients with no cancer coming back, no recurrence, and being able to keep the bladder intact if possible.

Dr. Gilligan: So for both of these trials, the question seems to be if we intensify treatment, can we increase the cure rate and keep patients cancer-free longer?

Dr. Grivas: That's exactly right, and that's the promise or the assumption of this trial, whether the addition of immunotherapy to chemotherapy and radiation can improve those chances.

Dr. Gilligan: What are the known risks that patients should be aware of?

Dr. Grivas: As Dr. Zhang mentioned before, every time we have the immunotherapy in clinical trials or in clinical practice, we have to do a good job educating, of course, all the medical providers, team members, and the patients for early recognition and reporting of what we call immunotherapy-related potential side effects. And as we discussed earlier, any organ of the immune system could be a target of an activated immune system. The reality is that if the side effects from immunotherapy happens, usually it's a mild to moderate degree and usually can be managed by holding of the immunotherapy drug and maybe sometimes give some steroids to cool down the immune system. Obviously, we need to be extra vigilant, and I always err on the caution of overeducated patients to avoid underreporting so we make sure we know ahead of time if a side effect happens.

Dr. Gilligan: Is there any reason to be worried that immunotherapy could make the side effects of chemotherapy and radiation worse?

Dr. Grivas: It's a great question, and we have to look in that during the course of the trial. The notion is so far, based on the available data, that it's safe to combine chemotherapy, radiation, and immunotherapy. There have been some early data suggesting that, and this is reassuring. At the same time, we need, again, to be extra vigilant, again, over-educating our patients to report any changes so we can be able to compare the potential side effects in the 2 groups. But so far, it seems to be a feasible strategy.

Dr. Gilligan: Good. And is this trial still open for patients?

Dr. Grivas: Yes, it is open and accruing patients actively, and I think it's a great opportunity for patients to discuss with their providers, urological oncologists, medical oncologists, radiation oncologists, whether they could be good candidates for this bladder preservation approach, if that's a good fit for them and the particular cancer at hand, and if so, whether they can be candidates for this trial or another trial called SWOG 1806, which is in the same space and setting.

Dr. Gilligan: And when might we expect results from the study?

Dr. Grivas: It may take time because this trial is still early in the accrual process. It may take a few years. The current estimate is probably 2026, so 5 years from now. However, the faster these trials accrue, maybe the faster is to have the results. So this might have been overestimation, but it depends with how quickly the study will accrue patients. It's a very exciting study and definitely, I encourage patients to discuss this and the SWOG 1806 with their providers.

Dr. Gilligan: Thank you very much. We're going to move on now, and Dr. Agarwal will tell us about the KEYNOTE-991 study. Dr. Agarwal, who is this study designed for?

Dr. Agarwal: This is a study which is designed for patients with newly diagnosed metastatic castration-sensitive prostate cancer. In simple words, this is for those patients who have been diagnosed to have a prostate cancer which has gone to different parts of the body.

Dr. Gilligan: And what's the current standard of care for these patients if they don't go on the study?

Dr. Agarwal: Fortunately, the current standard of care has gone through a paradigm shift in the last 5 to 6 years. It started with chemotherapy with docetaxel being approved for these patients in 2014 with 2 positive clinical trials showing benefit for docetaxel chemotherapy as far as improvement of survival is concerned. After that, 3 more drugs known as novel androgen axis inhibitors, so deeper blockade of androgen pathway, which is a driver behind prostate cancer progression. So these 3 drugs, abiraterone, or also known as Zytiga, enzalutamide, also known as Xtandi, and apalutamide, also known as Erleada. These 3 drugs and chemotherapy are currently approved agents for our patients with newly diagnosed metastatic prostate cancer.

Dr. Gilligan: And what is this study looking at to potentially change that or to add another option?

Dr. Agarwal: So this study is using the backbone of androgen deprivation therapy, which is standard testosterone suppression therapy, plus enzalutamide or Xtandi. And then patients who are receiving the standard of care therapy with standard testosterone suppression therapy, plus enzalutamide, they will be randomized to pembrolizumab versus placebo. Pembrolizumab is an approved immunotherapy for multiple cancer types and pembrolizumab, also known as Keytruda, works by activating our immune system to fight against cancer cells. In a way, this study is actually testing whether addition of this novel immunotherapy pembrolizumab to existing regimen of androgen deprivation therapy plus enzalutamide is going to improve survival outcomes.

Dr. Gilligan: What do we know about immunotherapy and prostate cancer?

Dr. Agarwal: So far, immunotherapy, as we call them, immune checkpoint inhibitors, many of them are approved for multiple cancer types. They have not been successful as single agents in the context of advanced prostate cancer. So this is a trial which is testing whether immunotherapy, the pembrolizumab is going to be effective in combination with enzalutamide and testosterone suppression therapy.

Dr. Gilligan: So patients will get the standard of care therapy either way. And then the question is, does adding immunotherapy make it even more effective than it is without it? Is that correct?

Dr. Agarwal: That's true. The primary end points of the trial are overall survival and radiographic progression-free survival, which basically means the investigators are going to look for improved survival, overall survival, and delaying of disease progression by adding pembrolizumab.

Dr. Gilligan: And we've already discussed the risks of immunotherapy on the previous 2 trials, but can you tell us again for patients who are particularly interested in this study what risks should they be aware of?

Dr. Agarwal: So pembrolizumab belongs to a class of drugs known as PD-1 or programmed death 1 receptor inhibitor. Usually, this class of drug, as a class, these are highly well-tolerated drugs and only a small number of patients, I would say less than 5% of patients, would develop grade 3 or 4 side effects which will require treatment with corticosteroids like prednisone. And those side effects usually happen when these immune checkpoint inhibitors are able to activate the immune system beyond desired limits. And when the immune system is activated to very high levels, the immune system can attack our own body and can result in diarrhea, skin rashes, liver enzyme abnormalities, and if not controlled in time can lead to hepatitis, which is inflammation of the liver, inflammation of the lungs causing pneumonitis or cough, dry cough mostly. So these are the common grade 3, 4 side effects which happen in up to 5% of patients with pembrolizumab.

Dr. Gilligan: Just for our listeners in case they're not familiar, when you talk about grades 3 and 4 toxicities, what should they understand that to mean?

Dr. Agarwal: In simple words, I would say grade 1 and 2 side effects are the ones which do not require any systemic therapy with steroids. Patients can go on with their daily activities without much problems. And mostly, these are controlled with medications which are over-the-counter. Even if we use prescription medicines, they're usually not able to affect the patient's overall lifestyle or quality of life. So these are the side effects which are pretty easily manageable mostly with over-the-counter drugs, symptomatic drugs, and patients lifestyle and quality of life are usually not affected by the side effects. And grade 3 and 4 side effects are those which require intensive therapy, in this context, with prednisone or corticosteroids sometimes requiring hospitalization and requiring multidisciplinary care with other specialists who are specializing in gastroenterology or pulmonology or on many other specialties. So that's how I would like to simplify the definition of grade 1, 2 versus grade 3, 4 side effects.

Dr. Gilligan: That's great. Thank you very much. Is the trial still open for accrual? Can patients still go on it?

Dr. Agarwal: Yes. Yes. Trial actually just opened for accrual, which is good news for our patients. And I would like to highlight that patients who have been diagnosed with newly diagnosed metastatic prostate cancer and they have started hormonal therapy like androgen suppression therapy, they still have 3 months to enroll in the trial. So if you have been diagnosed with metastatic prostate cancer and if you have started the treatment with testosterone blockade therapy, you can still go on the trial. You have 3 months to go on this clinical trial. And if you have started chemotherapy with docetaxel, which is a standard of care for our patients with this diagnosis, you can still go on the trial after receiving up to 6 cycles of chemotherapy with docetaxel. So this trial allows actually patients to go on the trial for up to 3 to 6 months after being diagnosed with metastatic prostate cancer.

Dr. Gilligan: So that's very helpful to know. At the conclusion of chemotherapy, they would then start the enzalutamide and either the pembrolizumab or placebo?

Dr. Agarwal: That's correct.

Dr. Gilligan: Well, great. And when do we expect to see results from the study?

Dr. Agarwal: So as we know this, which is great news for our patients, survival has gone up by almost 2 to 3 fourths over the last 10, 15 years, and in this disease setting, any trial takes up to 5 to 6 years to show results. So I estimate based on the available information on the ClinicalTrials.Gov website, the trial is scheduled to finish in 2026.

Dr. Gilligan: I see. Well, great. So thank you very much. Thank you all 3. That's hopefully a helpful summary of these 3 important new trials.

Dr. Agarwal: Yes, it's a pleasure to be here, Tim.

Dr. Grivas: Thank you so much.

Dr. Gilligan: Thank you. Thank you for listening to this podcast. There are many different clinical trials currently enrolling people with genitourinary cancers. If you're wondering whether participating in a clinical trial might be right for you, please talk to your health care team.

ASCO: Thank you, Drs. Gilligan, Zhang, Grivas, and Agarwal.

Visit www.cancer.net/clinicaltrials to learn more about participating in clinical trials. All treatments have side effects—please talk to your health care team about possible side effects to watch out for.

And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

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. 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 the data described here may change as research progresses.

In this podcast, Dr. Lidia Schapira and Dr. Daniel Mulrooney discuss a study published in the Journal of Clinical Oncology about mental health outcomes for AYA cancer survivors and how young survivors can get the mental health support they need after cancer.

Dr. Schapira is Associate Professor of Medicine at Stanford University School of Medicine and Director of Cancer Survivorship at the Stanford Comprehensive Cancer Institute. She is also the Cancer.Net Editor in Chief. Dr. Mulrooney is an Associate Member in the Division of Cancer Survivorship at St. Jude Children's Research Hospital. He is also the Cancer.Net Associate Editor for Pediatric Cancers.

View disclosures for Dr. Schapira and Dr. Mulrooney at Cancer.Net.

Dr. Schapira: Welcome to this Cancer.Net podcast. I'm Lidia Schapira, the editor-in-chief, and with me today is Dr. Dan Mulrooney, an expert in cancer survivorship in children's cancer. Welcome, Dan.

Dr. Mulrooney: Thank you, Lidia. Nice to be here.

Dr. Schapira: We have no disclosures for this podcast. And the article that was just published in JCO by Dr. De is what has prompted this conversation with Dan. In that article, scientists from Canada were interested in looking at the incidence and predictors of mental health outcomes among cancer survivors, of adolescent and young adult cancers. So they used a large database, and they looked at what happened to those adults who were diagnosed when they were between 15 and 21 years of age and had survived at least 5 years since their cancer. So they were now adults. What they were interested in were the mental health episodes that were either outpatient mental health problems, mostly anxiety, that were diagnosed in these cancer survivors and also, severe psychiatric episodes such as hospitalizations for a disease called schizophrenia and other important psychiatric illnesses. And they compared them to adults that were matched but did not have a history of cancer. And surprisingly, perhaps, or not so surprisingly, and this is what we'll discuss, they found that the survivors of cancer had more mental health problems. So there was a 30% higher rate of outpatient mental health visits, mostly for anxiety, and a 20% increased risk of a severe psychiatric episode as compared to these matched controls. So, Dan, I first wanted to get your reaction to this, and please feel free to correct my analysis if your interpretation was slightly different.

Dr. Mulrooney: No, it really isn't. Thank you, Lidia. It's a really important article concentrating on a group of survivors that we really already know are at higher risk for adverse mental health outcomes and psychosocial risks following their cancer therapy. But what's so interesting is they were able to combine large data sets. They were able to compare these survivors to the general population, which is very relevant for health care providers taking care of these patients in the community. And in addition to that, what I thought was particularly interesting is their ability to look at both outpatient visits and those more severe mental health issues that require an emergency room visit or require admission to the hospital. I think this is very informative information about this high-risk group of survivors and hopefully will be instructive if we can interpret this and turn this into services that we can direct to these patients.

Dr. Schapira: I found it interesting, Dan, also that they said that they only captured the mental health visits in the outpatient setting that were delivered by physicians because of the data. So, in fact, visits with social workers or psychologists did not even make it into these statistics. And that suggests to me that there may be even more problems that were not captured by these numbers.

Dr. Mulrooney: I think you're absolutely correct on that. If anything, these numbers are an underestimate of the issues and the problems that may be out there. It's only those that made an appointment and went to a mental health care provider. They missed social workers. They missed other social networks, ministers, religious organizations that might be providing help as well. And of course, we're talking about a young adult population that may not always reach out for these services. And so, this group did reach out. So we probably have the more severe group represented here, but we're missing a large population underneath this. I suspect you're absolutely right.

Dr. Schapira: And so, if we think about what we can do with his information, how we can think about guidelines, assessments, and support, let's think back to when these young adults and adolescents are first diagnosed. I was also struck by the fact that there was a difference with more mental health problems in those treated in adult cancer centers than those that were treated in pediatric cancer centers. Can you tell me what may account for those differences?

Dr. Mulrooney: That's a very interesting question and fact that came out of this paper. And I suspect there are probably a number of reasons. I think globally, this paper looks at mental health issues in cancer survivors, which we have to separate from mental health issues in patients going through active cancer therapy. There may be quite a bit of overlap. There may be some similarities. But I suspect, particularly in the AYA population, the issues that they encounter as a survivor are different than those that they struggled with maybe as a patient. And they saw this difference, particularly for outpatient visits, based on where they were treated. One thing to point out is the majority of these survivors were actually treated in the adult cancer centers. Because in Canada, if you're over age 18, you're considered an adult and you're treated at an adult cancer center. So there was a smaller population, I think it was only about 25% to 27%, that were actually treated in pediatrics. And certainly, the focus and the culture of care is different between pediatrics and adult medicine. And I suspect there may be some differences in survivorship support and care. And these survivors, they were relatively soon after receiving their care and those in the pediatric community are probably receiving, I suspect, maybe more follow-up, a survivorship program, probably a little bit more structured, and hopefully a survivorship program that has social work support or psychosocial services provided. Now, I can't say that the adult centers don't have that, but of course, the population is much larger, and the visits and that culture is very different than they receive in pediatrics. So it is possible that some of those early services and supports are just not available to that population.

Dr. Schapira: So let me pick your brain about this a little bit since you are immersed in this world. What does it take in your mind to create the best possible environment for these young adults to thrive after cancer or to have an opportunity to receive all the mental health support that they need in order to move on with their lives?

Dr. Mulrooney: I think number 1 is to recognize it as an issue. In particular, we know that this AYA population is considered a high-risk population for mental health issues after cancer. And so number 1, we really need to recognize that. And this paper draws our attention to that very nicely, that it is an issue, there's a high prevalence of mental health issues after cancer therapy. But in our survivorship clinics, we need to address the medical and chronic health concerns after cancer therapy, but we can't forget these psychosocial issues. And how does that affect this individual survivor? They're struggling with lots of issues after cancer: fear of recurrence, fear of a second cancer, maybe body image issues, maybe health conditions that their peers at this age are not encountering. And so in addition to treating those and doing appropriate surveillance, we should really also be doing mental health surveillance and screening, and identifying appropriate referrals for them to address those issues.

Dr. Schapira: So, Dan, how do people like us who are not trained in mental health, what should we be doing and thinking about as oncologists or even as primary care physicians who see these patients? What can we do?

Dr. Mulrooney: Yeah, I thought a great deal about that when reading this because even in primary care, there's at least some general screening for mental health or depression. Most primary care providers, at least mine, hands me a little questionnaire that I fill out while I'm in the waiting room. Obviously we need to do that, but perhaps we need to take it a step further in this unique population, to maybe ask the appropriate questions in a survivorship clinic. Hopefully, we have social work support. Not all centers will have that. Obviously, there's going to be access issues. And in the United States here, there's probably financial issues that maybe didn't occur here in Canada. But we really need to advocate for taking those questions a little bit further, digging a little bit deeper, and really having a social worker available, maybe to do that screening in person, maybe not do it on paper in a group that we know is high risk.

Dr. Schapira: So that was 1 of the things that I also thought about as I was reading this, this idea that screening tools are great, when you think that what you're screening for has a relatively low prevalence. But if, in fact, this is so important, maybe an assessment done by a professional who's trained may actually take us a little bit further and help us so that we don't miss people. I know many screening efforts, for instance, where the data is captured, but then there is no link to a solution or a referral. And it's not that people don't mean well, but there are all sorts of reasons why things fall through the cracks, which is sad. Whereas if there were a relationship and an assessment done by a professional, I feel then we would be more-- our default would be more to ask, to support, and to keep asking. Because 1 of the things I think the authors also tell us is, you need to keep doing this over the course of many years. Is that your understanding as well?

Dr. Mulrooney: Absolutely. All of us were trained as oncologists, and we feel like we maybe don't have the skills to address this. But we certainly have the ability to ask and delve a little bit deeper. We know how to take a history, we know how to-- we take care of patients in very critical realms. And so we certainly are comfortable asking difficult questions. And mental health questions should be really no different from that. And, an important thing I noticed in this paper is 1 of the predictors of a mental health issue for the survivors was a preceding mental health issue even before diagnosis or going through therapy. So are we missing them all the way along? And maybe we should be intervening or addressing this when they're our patients in our cancer center, and then not miss that transition to appropriate survivorship care, and appropriate psychosocial care after that.

Dr. Schapira: I couldn't agree with you more. I think between the 2 of us, we could design the perfect cancer care system, right, where we reach out to these adolescents and young adults. And, in some cases, I imagine in the younger ones, there's also the parents to consider at the time that they're getting treated, right? And then maybe those relationships as they grow into adulthood also change. And there may be, sort of, a disruption in what we think of as the family unit or the supports available to that young person so it's very complicated. Do you have any advice, given the work that you do in this survivorship clinic that you've had, how can we even begin to do this? To reach out to everybody and make sure that people feel connected to you, but then also that when you let them go, that they can find the support they need?

Dr. Mulrooney: What a struggle it is, particularly with these young people who are growing into their own, becoming more independent, want to take more responsibility, but then are struggling with so many of these health care issues, whether they're physical or mental. And family support and the family unit has to be considered, particularly with the younger population. And not only the mental health of the survivor, but the mental health of the parents or the family who may have their own issues preceding cancer therapy, or may be struggling with how to take care of my child after cancer, or this fear of recurrence themselves. And oftentimes the parents may have a harder time than the young person does. And we have seen both, post-traumatic stress disorder, but also post-traumatic resilience in some of these patients. They really feel they've come through something and it's made them stronger and it's changed their outlook on life. In our clinic, we make sure that we at least have them see a social worker when they come into the survivorship clinic, and then again, as there may be mid-adolescence and a year or 2 before they're going to graduate or leave our care. So that we're addressing those issues or identifying those issues. And then that gives us at least a year or 2 to try to find the services locally, wherever they live, for them. The handoff in that transition is very difficult. And I won't lie, I've been concerned about the transition for a long time, as you know. I think it's an area we really need to improve upon. We need more buy-in from the medical community across the board, maybe more research in that area.

It's a real struggle, but we can't just finish their survivorship care and not make sure that they're not connected again locally because the care continues, and the paper showed that that the risk continued to increase and went up with time from diagnosis. So it's a real struggle, it's just really hard.

Dr. Schapira: You just described the challenge that we all face so beautifully. And so, my final question to you is about your experience with young cancer survivors during this last year, with the COVID pandemic. With the isolation and all of the mental health issues that we've heard about just among young people in general, what have you found? I imagine you're going to tell me that there is enormous variation, but I'd love to have you share with our listeners a little bit of what you've learned.

Dr. Mulrooney: It has increased the stress on cancer survivors, and it's made-- the pandemic's made life difficult for everybody. But again, now if we're talking about a population who has survived cancer, who may have some chronic health effects related to that, and they've called us and they said, "Am I at increased risk? What should I do? Do I need to do something different to protect myself?" And so far, we don't know. The data really aren't mature enough to understand if a survivor of cancer is at a higher risk than somebody in the general community. Certainly, if they're on immunosuppressive medications or certainly if they have chronic health conditions, we suspect they're at higher risk, just as you might see in the community, but particularly with an older population.

Access to care is certainly more limited, and so issues, just as we're talking about here, mental health services are magnified, and it's harder to reach out and get those services. I was thinking a great deal about that when reading this because, in some ways, they may be able to get services a little bit more quickly because it's all being done by telehealth, and these encounters are probably not being done in person. On the other hand, it's disrupted scheduling and access. So, again, I worry that there's a large population that was missed even in this study, but a large population now that's being missed and not receiving services because of the pandemic. Hopefully, as this begins to ease, we can start attacking that problem and getting to more and more of those people.

Dr. Schapira: Are there resources for survivors, especially now in the time of the pandemic, someplace they can turn to if they want to learn more about this topic?

Dr. Mulrooney: There are a number of resources, and particularly with the Children's Oncology Group, has developed what they call Health Links and documents in lay language that can be a resource for survivors who are struggling with physical illness and also mental health illness. The website is called survivorshipguidelines.org, and the link is to the Health Links on that page. There's a Health Link particularly for mental health issues following cancer, and also 1 for issues related to the COVID pandemic that I hope survivors might find helpful.

Dr. Schapira: Well, thanks, Dan, it's been lovely chatting with you. It always is. I know I've learned a lot and I hope this is useful to our listeners as well. Thanks for everything and thanks for all you do every day.

Dr. Mulrooney: Thank you very much. It was nice to be here.

ASCO: Thank you, Dr. Schapira and Dr. Mulrooney. Find more resources for young adults at www.cancer.net/aya. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough 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. 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 the data described here may change as research progresses.

In this podcast, Cancer.Net Associate Editor Dr. Norah Lynn Henry discusses new research presented at the 2020 San Antonio Breast Cancer Symposium, held virtually December eighth through eleventh. 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. View Dr. Henry's disclosures at Cancer.Net.

ASCO would like to thank Dr. Henry for discussing this research.

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 from the 2020 virtual San Antonio Breast Cancer Symposium. My institution enrolled patients in the first trial that I will discuss, otherwise, I have no conflicts of interest for any of the trials that I will talk about.

Today, I'm going to focus primarily on treatment of non-metastatic breast cancers that are hormone receptor-positive and HER2-negative. These studies highlight personalizing treatment for individual patients. In the first and last trials I will mention, the studies examine whether it is possible to give less treatment without substantially increasing the risk of breast cancer recurrence. In general, giving less treatment leads to fewer long-term toxicities and better quality of life. In contrast, the other 2 trials I will mention are examining adding more therapy to standard treatment with the goal of increasing breast cancer cure rates for patients at high risk of recurrence without causing too much additional toxicity.

One of the biggest stories in this meeting was the result of the RxPONDER trial. This trial enrolled thousands of women with hormone receptor-positive, HER2-negative breast cancer, who had cancer present in 1 to 3 lymph nodes under her arm. The standard treatment for patients who have lymph node positive breast cancer has been to recommend chemotherapy in addition to anti-hormone therapy. This trial is testing whether that is actually the best treatment. In this trial, every patient's tumor was tested with a test called Oncotype DX and was given a recurrence score ranging from 0 to 100, depending on how quiet or aggressive the tumor is. Women whose tumors had a score between 0 and 25, which is at the low range, were randomized, like flipping a coin, to either receiving the standard, which is chemotherapy followed by anti-hormone therapy, or to just anti-hormone therapy alone.

The patients were then monitored to see if they developed recurrence of their breast cancer. Overall, there was no difference between the groups. Meaning that adding chemotherapy to the treatment did not provide a benefit in terms of reducing risk of recurrence. When they divided the groups by lower or higher score, it still didn't make a difference. However, when they divided the women by menopausal status, it did. Women who were post-menopausal when they were diagnosed with breast cancer did not get any benefit from chemotherapy. In contrast, women who were pre-menopausal did get a benefit from chemotherapy. And in fact, they lived a little longer than those who only got anti-hormone therapy. However, there's still a question about how much of the benefit is from the chemotherapy itself acting directly on the cancer and how much is from the chemotherapy putting the ovaries to sleep, which also treats the cancer, although indirectly.

Therefore, the take-home message for a post-menopausal woman with hormone receptor positive, HER2-negative breast cancer who has 1 to 3 involved lymph nodes, is to talk with her oncologist about whether her tumor should be tested to help make a decision about chemotherapy as opposed to just assuming that she needs chemotherapy because her lymph nodes have cancer in them. For pre-menopausal women, it's a little less clear, unfortunately. In that case, it is important to talk about the pros and cons of chemotherapy with her oncologist depending on her exact situation, including her age and the amount of cancer in the breasts and the lymph nodes. Hopefully, we will learn more about how best to treat pre-menopausal women when additional analyses are performed on the data from this trial.

Also related to non-metastatic hormone receptor positive, HER2-negative breast cancer, updates on 2 trials related to the use of adjuvant CDK4/6 inhibitors on patients with high risk to breast cancer recurrence were presented. The CDK4/6 inhibitor medicines are routinely used to treat patients with metastatic breast cancer since the combination of these drugs plus anti-hormone therapy results in longer time to disease worsening compared to just anti-hormone therapy alone. Therefore, these drugs are now being tested in the non-metastatic setting to see if they increase the likelihood of cure of breast cancer.

In the first trial called MonarchE, addition of abemaciclib, which is a CDK4/6 inhibitor, to standard aromatase inhibitor therapy decreased the likelihood of recurrence of invasive disease in patients at high risk of disease recurrence. However, the length of follow up of the patients who participated in the trial is still rather short, and so far, adding the treatment has not shown that people will actually live longer. The other trial that was presented, called PENELOPE-B, studied a similar CDK4/6 inhibitor medicine called palbociclib in a similar setting. In that trial, although the benefits looked promising early on, with longer follow up, the benefits have unfortunately disappeared. Therefore, although the results of MonarchE look very promising, we still need more follow up to determine the actual benefit to patients. Also importantly, this drug is not currently approved for treatment of early stage breast cancer at high risk of recurrence, and it is not currently included in treatment guidelines. So at this point, it is unlikely that the drug costs will be covered. We await additional updates from these and other trials of similar design in order to know whether patients should be receiving these drugs as part of their breast cancer treatment.

And finally, to change gears a little to patients who are at low likelihood of disease recurrence, we also got an update of the PRIME II trial. This trial asked whether radiation therapy is beneficial in women over the age of 65 who have small lymph node-negative, hormone receptor-positive breast cancer. In this trial, most patients had tumors that were smaller than 2 centimeters, and all underwent lumpectomy and were planning to take adjuvant anti-hormone therapy. Patients were randomized either to receive radiation therapy or to not receive radiation therapy. Radiation therapy is the standard of care in this setting. Consistent with their earlier results, not having radiation therapy did increase the risk of local recurrence a little from 1% to 10% over 10 years. And this really highlights that although the risk of local recurrence in the breast is a bit higher if a patient does not have radiation therapy, it still has a 90% chance of not having a recurrence during that 10-year period. Also, not getting radiation did not affect survival from breast cancer. It is important to note that most patients likely took endocrine therapy, and it is thought that risk of recurrence is higher if both radiation therapy and endocrine therapy are omitted. Therefore, patients over the age of 65 or 70 who have small hormone receptor-positive breast cancers should talk with their surgeon, medical oncologist, and radiation oncologist about the benefits and risks of radiation and make a personal decision about whether or not to undergo radiation therapy.

Well, that's it for this quick summary of this important research from the 2020 virtual San Antonio Breast Cancer Symposium. Overall, we continue on a fast track in breast cancer with many new and exciting therapies being actively studied and research helping support our patients do better than ever before. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you.

ASCO: Thank you, Dr. Henry. 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.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough 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. 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 the data described here may change as research progresses.

In this podcast, Cancer.Net Associate Editor Dr. Michael Williams talks about new research and advances in the field of lymphoma, including 3 recent U.S. FDA drug approvals. The research discussed was presented at the 2020 American Society of Hematology Annual Meeting, held virtually December fifth through eighth. Dr. Williams is the Chief of the Hematology/Oncology Division and Director of the Hematologic Malignancies Program at the UVA Cancer Center. He is also the Byrd S. Leavell Professor of Medicine and Professor of Pathology at the University of Virginia School of Medicine. View Dr. Williams' disclosures at Cancer.Net.

Dr. Williams: Hello. This is Dr. Michael Williams. I'm professor of medicine at the University of Virginia Health System in Charlottesville, Virginia, and I'm pleased to welcome you to this podcast for Cancer.Net. I'm reporting on some of the exciting updates that were just presented at the American Society of Hematology Annual Meeting. Typically, this is a meeting of 30 or 35 thousand clinicians and investigators from around the world. This year, as with so many meetings, we met virtually, but I would say very successfully done. Lots of exciting new data, and I'll try to give you a glimpse of what some of the progress has been. Before I start, I'll mention a few disclosures. So I have research grants that are awarded to the University of Virginia for clinical research from Celgene, Janssen, Pharmacyclics, and TG Therapeutics. And I have served as a consultant for Celgene, Janssen, and Pharmacyclics, as well as Kyte Pharmaceuticals, which is a division of Gilead.

So the advances this year weren't just at the meeting. There were 3 new drug approvals in the past 6 months for lymphoma. Tazemetostat, which is an EZH2 inhibitor, was approved for relapsed/refractory follicular lymphoma patients who have a mutation in a gene called EZH2. So they showed good tolerance of this treatment with high response rates in these patients with the mutation. So it provides another important treatment option for people with relapsed follicular.

A new approval for relapsed diffuse large B-cell lymphoma was a novel monoclonal antibody called tafasitamab given in combination with lenalidomide that also showed good responses and generally very good tolerance in people with relapsed aggressive lymphoma. So a welcome addition again to our treatment options. And then finally, a chimeric antigen receptor T-cell therapy or CAR-T was approved for relapsed/refractory mantle cell lymphoma. And I will say a bit more about that agent as we get into the discussion about CAR-T therapy for mantle cell.

The first abstract presentation that I want to mention is in chronic lymphocytic leukemia or small lymphocytic lymphoma which, of course, is really 1 disease. It's just a spectrum of whether you have more of a leukemic phase or a lymph node enlargement component to your disease. Treatment in CLL has really shifted in recent years away from cytotoxic chemotherapy and is now well established that most patients needing treatment, whether for newly diagnosed disease or for patients who have been previously treated with other regimens, that targeted therapies such as Bruton tyrosine kinase inhibitors or a BCL-2 inhibitor venetoclax can get very high response rates.

There's been interest among many groups in testing combinations of targeted drugs, and we heard an update of a report called the CAPTIVATE study that combines ibrutinib plus venetoclax. Both of these are oral agents. As a randomized study for patients with CLL who need treatment and have not been previously treated for their CLL. And what this study did was provided a combination of the 2 drugs as first-line therapy, and they showed that after a period of about 12 cycles of combined treatment, that you had very, very high remission rates. They used a very sensitive method, a molecular method, to detect minimal residual disease. And if patients were in a deep molecular remission, so undetectable MRD at the end of treatment, they were randomized to continuing with either no therapy or with just ibrutinib alone. And it was found that after a year, there was really no difference. So it shows that with combination therapy, you can get a deep enough remission to have a durable and ongoing response for those patients. They also randomized those who still had detectable residual disease to either ibrutinib alone or a combination of ibrutinib plus venetoclax, and they showed that their outcome at the end of treatment was likewise similar. So it shows a very good non-cytotoxic-chemotherapy-based approach to treatment of chronic lymphocytic leukemia, small lymphocytic lymphoma.

So the second item I wanted to bring your attention was for another form of indolent or low-grade non-Hodgkin lymphoma called Waldenstrom macroglobulinemia which is also identified as lymphoplasmacytoid lymphoma. And in this study, they used a combination of ibrutinib plus rituximab, an anti-CD20 monoclonal antibody, versus placebo with rituximab alone. So this study is reporting now long-term follow-up with more than 5 years since the onset of treatment initiation in 150 patients. So rituximab by itself was a standard of care for patients with Waldenstrom at the time the study was designed. We now know that ibrutinib can give very good responses, especially when given in combination with rituximab. And indeed, they showed that now with 5 years of follow-up, that the response in terms of the serum IgM level, which is a marker for activity of this disease, improvement in anemia as well as objective response rates were much improved with the combination of ibrutinib plus rituximab versus rituximab alone. They also showed that there was a delay in the time that a patient needed another line of therapy for progressive disease when they had that combination. So important long-term follow-up there confirming the safety and activity of ibrutinib and rituximab for that disease.

And then finally, I'll give an update on 1 of many reports at this meeting on CAR-T cell therapy. So just to remind those of you who may not be so familiar with this, it's a technique of cellular therapy, wherein a patient who's got disease progression with follicular lymphoma or mantle cell lymphoma or diffuse large B cell lymphoma, the patient undergoes a procedure where T-cells are removed from their blood, and then in the laboratory, they are reprogrammed to attack the patient's lymphoma cells. So the reprogramming is done, the CAR-T cells, the chimeric T-cells are expanded, and then shipped back to the treating center where the cells are infused intravenously to the patient. There is already an approval of CAR-T cell therapy for diffuse large B-cell lymphoma as I mentioned. It is now approved CAR-T called axicabtagene ciloleucel or axi-cel is approved for mantle cell lymphoma, and what we heard at this in Boston. She gave an update on treatment of relapsed refractory follicular lymphoma and marginal zone lymphoma with the axi-cel CAR-T.

So what Dr. Jacobson and her colleagues reported was for patients with relapsed and refractory follicular lymphoma, the overall response rate was 95%, with 80% of these patients being in a complete remission with ongoing follow-up. In those with marginal zone lymphoma, the numbers of patients treated were smaller, but they also showed high-response rates, 85% with 60% achieving a complete remission. And at a year of follow-up, most patients were remaining without evidence of disease progression. So a very promising advance in follicular lymphoma. It also raises the possibility that we may be able to use CAR-T cell therapy instead of traditional autologous stem cell transplantation for relapsing patients.

But this is something that will have to be tested in formal clinical trials before becoming established as a new standard of care. So by the end of the meeting, it was clear that progress continues at a very rapid pace across the fields of human logic malignancies, lymphomas, leukemias, multiple myeloma, and others. So it reminds us that it's important if you're dealing with 1 of these disorders that you make sure you've done your due diligence in getting another opinion if that's warranted, at seeking out clinical trials which help bring some of these most promising therapies to the clinic and help us advance the progress in treatment as rapidly as possible. So I'd like to thank you for your attention today and wish you all the very best in the year ahead.

ASCO: Thank you, Dr. Williams. 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.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough 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. 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 clinical trials described here may no longer be enrolling patients, and final results are not yet available.

Before any new cancer treatment can be approved for general use, it must be studied in a clinical trial in order to prove it is safe and effective. In today's podcast, members of the Cancer.Net Editorial Board discuss 3 clinical trials that are exploring new treatment options across prostate, bladder, and kidney cancer.

This podcast will be led by Dr. Timothy Gilligan, Dr. Neeraj Agarwal, Dr. Tian Zhang, and Dr. Brian Shuch.

Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig Cancer Center. He has no relevant relationships to disclose.

Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. He has served in a consulting or advisory role for Janssen and Bristol-Myers Squibb.

Dr. Zhang is an assistant professor of medicine at Duke University School of Medicine and is a medical oncologist at Duke Cancer Institute. She has served in a consulting or advisory role for Janssen and Bristol-Myers Squibb.

Dr. Shuch is the director of the Kidney Cancer Program at UCLA Health and the Alvin & Carrie Meinhardt Endowed Chair in Kidney Cancer Research at the institution. He has served in a consulting or advisory role for Bristol-Myers Squibb.

View full disclosures for Dr. Gilligan, Dr. Agarwal, Dr. Zhang, and Dr. Shuch at Cancer.Net.

Dr. Gilligan: Hi, I'm Dr. Timothy Gilligan from the Cleveland Clinic Taussig Cancer Institute. I'm joined today by Dr. Neeraj Agarwal from the Huntsman Cancer Institute and the University of Utah and Dr. Tian Zhang from the Duke Cancer Institute and Brian Shuch from the UCLA Institute of Urologic Oncology. Today, we're going to discuss 3 ongoing trials in prostate cancer, bladder cancer, and kidney cancer. As you may know, clinical trial are the way that doctors are able to find better treatment for diseases like cancer. Patient participation is vital for clinical trials. By participating in the clinical trial, you can directly help researchers develop better treatment, reduce side effects, and even reduce the risk of cancer altogether. The 3 trials we'll discuss today were chosen by members of the Cancer.Net Editorial Board Genitourinary Cancers Panel from the trials in progress abstracts that were presented at ASCO 2020 Genitourinary Cancers Symposium. Because these are ongoing clinical trials, final results from these studies are not yet available. I'd like to note that none of us have any direct involvement in any of these trials. To view our full disclosures, please visit the show notes for this episode on Cancer.Net. We're going to start with Dr. Agarwal and a study looking at prostate cancer, the MAGNITUDE trial. [A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Participants With Metastatic Prostate Cancer (MAGNITUDE)] Dr. Agarwal, can you tell us a little bit about this study?

Dr. Agarwal: This is a large phase III trial of 1,000 patients. This trial includes patients who have progressive, metastatic, castrate-resistant prostate cancer and have never received any other systemic therapy for their castrate-resistant prostate cancer.

Dr. Gilligan: Why don't we clarify for listeners what we mean by castrate-resistant prostate cancer? Who are these patients?

Dr. Agarwal: When patients present with advanced prostate cancer which has [spread] to different parts of the body, that is called metastatic prostate cancer. And the most effective strategy, which is the backbone of treatment of these patients, is androgen deprivation therapy or castration therapy, which blocks the production of testosterone from the gonads. At this point of time, utilizing medical castration [with drugs] or surgical castration can effectively slow down the progression of cancer.

Dr. Gilligan: So these are patients who are already on first-line hormonal therapy to lower their testosterone level?

Dr. Agarwal: Yes. Once they start progressing on this first-line castration therapy, we call this state to be castrate-resistant prostate cancer. So this is the patient population which is having disease progression on first-line therapies for the advanced prostate cancer, and now, testosterone levels are low, but still, the prostate cancer is progressing.

Dr. Gilligan: So what's the current standard of care for this population of patients who are progressing on first-line hormonal therapy?

Dr. Agarwal: In the last 2, 3 years, the treatment of castration-sensitive prostate cancer, which is the newly diagnosed advanced prostate cancer we were just talking about, has changed dramatically. Multiple drugs which are being used, or were being used, in the castrate-resistant prostate cancer have moved to the setting of castration-sensitive prostate cancer. Having said that, many patients with castration-resistant prostate cancer have not yet received any of those drugs. So as an example, in this clinical trial, a patient could have received chemotherapy with docetaxel in the first-line therapy setting or a newly-diagnosed metastatic prostate cancer setting. But then when they have disease progression, the most commonly utilized medications are either abiraterone or enzalutamide, both are oral pills, we call them novel hormonal therapies. So those are still the backbone of treatment for castrate-resistant prostate cancer.

Dr. Gilligan: So for patients going on this study, what would the treatment be on the trial?

Dr. Agarwal: Patients will be randomized to treatment with abiraterone, which is a novel hormonal therapy, plus prednisone, which is utilized with abiraterone to negate the side effects of abiraterone, plus/minus a new class of drug known as a PARP inhibitor. And in this trial, the drug which is being used is called niraparib. Niraparib is a novel drug, a PARP inhibitor, and just to elaborate a little bit more on PARP inhibitors, this class of drug have recently been approved [to treat patients with] the later phases of castrate-resistant prostate cancer. So 2 drugs, olaparib and rucaparib, were recently approved by FDA in those patients who have had disease progression on novel hormonal therapy plus/minus docetaxel chemotherapy, so for pretty late phases of prostate cancer or castrate-resistant prostate cancer. In this trial, a PARP inhibitor is being moved upstream so that patients don't have to wait for disease progression or novel hormonal therapy or chemotherapy in metastatic castrate-resistant prostate cancer, and they will have the availability of this drug upfront in this setting of newly diagnosed metastatic castrate-resistant prostate cancer.

Dr. Gilligan: When this drug is used in the more advanced setting, it's limited to patients who have particular mutations. Is that the case in this study as well?

Dr. Agarwal: This trial is targeting the strategy to 2 different patient populations. So 1 patient population is that [in which the] tumor has defects or mutations in the DNA repair genes. We call them homologous recombination repair mutations. I put it simply, DNA repair gene mutations. So there is a cohort of patients, a group of patients, among these 1,000 patients, who will harbor DNA repair gene-related defects in the tumors. And there is another cohort of patients who do not have to have those defects, and we call them unselected patients. This trial is enrolling both groups of patients, and, in fact, the patients' unselected cohort has actually completed accrual. So the trial is now only looking at those patients who are harboring DNA repair gene-related defects in the tumors. Just to complete the story in this context, as you said, the drugs olaparib and rucaparib, which have already been approved in the later phases of castrate-resistant prostate cancer, they are only approved for patients who are harboring DNA repair defects.

Dr. Gilligan: So for the patients who can go on the trial now, who have these defects, the question this trial is asking then is, does it help to use this treatment earlier on rather than waiting until later?

Dr. Agarwal: Absolutely. So given these are oral therapies, reasonably well tolerated, better tolerated than traditional chemotherapies, it makes sense to move these oral pills to upfront or earlier settings where more patients can be candidates for these drugs which can be taken at home, and these patients don't have to have disease progression on chemotherapy to [receive] these medications. Just to complete, Tim, I just want to add that there are 2 endpoints of this trial. One is radiographic progression-free survival, which is the primary endpoint, and the secondary endpoint is overall survival and many other endpoints we'd like to see, like pain progression or toxicities and so on. Radiographic progression-free survival means how long these drugs or drug combination is able to contain the disease from progressing [or worsening] as detected by the scans. We hope that this trial will show delayed progression on the novel combination compared to abiraterone.

Dr. Gilligan: Thank you. So one last question, are there any known risks that patients should be aware of? What are the side effects of this class of medication?

Dr. Agarwal: Yes. Two major side effects. Every drug has side effect. And so do niraparib and abiraterone. So abiraterone is already approved for patients with metastatic castrate-resistant and castration-sensitive prostate cancer. So I'm not going to elaborate much on abiraterone. Regarding niraparib, this class of drug, including olaparib and rucaparib which I earlier mentioned, they have this class of side effects, which belong to this class of drugs. And 1 of the most common side effects is anemia, which is low hemoglobin, and which happens because these drugs can also slow down the replication of red [blood] cells. Other less common side effects are decrease in the platelet counts and decrease in the white cell counts. But they happen with much lesser degree compared to anemia. Another common side effect is nausea. Nausea and vomiting can happen, and we have to keep an eye on nausea and vomiting because the side effect can easily be prevented or treated with anti-nausea medications. There are many other side effects which are less common, and I won't get into them, but these are the 2 most common side effects, which are fortunately easy to handle in the clinic.

Dr. Gilligan: And I just want to repeat what you said before that there is accrual still going on for the study, but it's limited to patients who have particular mutations in their cancers.

Dr. Agarwal: Yes. So currently the study is not accruing for those patients who do not have those DNA repair general-related events. But it is still accruing patients, looking for patients who are known to have those mutations in the prostate cancer.

Dr. Gilligan: What proportion of patients with prostate cancer have these kinds of mutations?

Dr. Agarwal: Depending upon the study, I would say up to 20% of patients can have DNA repair gene-related defects in their tumors. So it is very important to bring this up with our clinical or medical oncologists who are treating patients with metastatic or advanced prostate cancer, and especially with approval of 2 drugs, it is very important that every single patient who is deemed to be a candidate for treatment with this class of drug, PARP inhibitor, undergoes comprehensive genomic profiling or simply speaking, mutation testing of their prostate cancer tumors.

Dr. Gilligan: Thank you. And I think that's worth emphasizing. This is an example of personalized cancer care based on the genomics of the individual's tumor which is happening more and more, and as Dr. Agarwal said, if you have metastatic prostate cancer, we are recommending a standard of care that people get genomic testing now. So this is an example of a step in that direction. So thank you, Dr. Agarwal.

Dr. Zhang, why don't we move on and talk about the bladder cancer trial that you were going to discuss, the PROOF 302, that also has a personalized genomic component to it, I believe. [Study of Oral Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations]

Dr. Zhang: In bladder cancer, we've come to a place where the genomic profiling is very important to find FGFR mutations or fusions, and this subset of patients that have FGFR mutations or fusions, these patients tend to have good responses to now standard of care treatments in the metastatic setting. And this particular trial is looking at using a drug called infigratinib in this patient population, specifically targeting that FGFR and inhibiting it. This is a trial in the adjuvant setting for patients who have urothelial cancer of either the bladder or of the ureters and upper tract who received surgery and then go onto this trial or treatment with infigratinib versus a placebo.

Dr. Gilligan: Can you spell out for our listeners who the group of patients are who are going to be eligible for the study?

Dr. Zhang: Sure. These are patients who have already undergone surgery for either their bladder cancer or an upper tract tumor. And so these are patients in that 4-month window after surgery, who have already had their surgeries, and it's either for patients who have had prior chemotherapy before their surgeries or not with higher-risk features defined based on each of those populations. But it is for a higher-risk patient population that have a higher risk for having disease recurrence and spread of their urothelial cancers after surgery. In this setting, we really don't have any approved adjuvant treatments. And so the point of this study is really to try to prevent disease recurrence.

Dr. Gilligan: I want to clarify 1 thing. My understanding was for these patients who have not had preoperative chemotherapy, they are not patients who were considered eligible for postoperative cisplatin-based chemotherapy since that is often used in the adjuvant setting. Is that correct?

Dr. Zhang: That's absolutely correct, Tim, and thanks for pointing that out. So if patients had not received preoperative chemotherapy, they have to be ineligible for cisplatin-based chemotherapy, which we would often recommend in the postoperative setting. But if they are not eligible for chemotherapy after surgery and have these higher-risk features, then they would qualify for this study.

Dr. Gilligan: I think it's important for patients to understand that because if considering going on this trial, the standard of care would be just to watch. And so what it's asking is, can we do something instead of just watching that would lower the risk of relapse or worse outcome with the cancer?

Dr. Zhang: Absolutely. I think we always try to recommend proven strategies first, and in this particular case, the recommendation for somebody who is a candidate for chemotherapy after surgery would still be to go with chemo first.

Dr. Gilligan: The genetic testing that will be done to determine eligibility for the study, can you say a little bit more about that?

Dr. Zhang: Sure. My understanding is that the study will take most genomic tests that are currently commercially available, but they have to fulfill the criteria of having FGFR mutations and/or fusions in the tumor in order to go on the study. So we often now will send the surgical specimens for genomic testing, especially in our higher-risk patients that are defined like the study defines. And so that particular patient population, because they're at higher risk for recurrence, we try to identify these FGFR mutations and fusions early on so that we can know whether the standard treatment for these patients would be an option later on.

Dr. Gilligan: Are there cost implications of that for the patients?

Dr. Zhang: Certainly, now some of the commercially available genomic testings are approved by insurance and are billable through insurance, but patients may be responsible for a copay. I want to add 1 more thing about the drug itself because I do think there's some interesting activity of infigratinib that has been published in the last year, and that is in the earlier-phase studies of infigratinib in the metastatic setting, in the more advanced urothelial cancer settings, we saw pretty high response rates as well as disease control rates, particularly in patients who had disease in the upper tracts, so in the ureters and above. And so I think it's promising and potentially very interesting to study this for patients who have had disease removal, and surgeries.

Dr. Gilligan: That's an important point for listeners to understand, that this is an exciting new class of drugs and in patients for whom this treatment is appropriate, we're seeing very good response rates in more advanced disease settings, and there's a natural progression. When we see it work in the advanced setting, we try to move it to an earlier setting to see if we see a similar or greater benefit. As Dr. Agarwal was saying about prostate cancer, we've found a number of times that using drugs earlier works better. This is another example of studying that to see if that's the case here.

Dr. Zhang: I absolutely agree.

Dr. Gilligan: What should listeners know about potential risks or side effects for this class of treatment?

Dr. Zhang: FGFR inhibitors like infigratinib have a class effect, and I think the main toxicities that we've come to see are skin toxicities and nail toxicities, as well as there are some eye toxicities as well. So particularly for patients who are going on these types of treatments, we often will recommend baseline eye exams, and then to follow them on treatment, particularly for any blurry vision or other vision changes that arise. And 1 of the class effects of these FGFR inhibitors is also to cause increases in phosphorus levels [in the blood], and that is due to their inhibition in the renal tubules to prevent phosphorus excretion. And so there was a recent publication also that for patients who develop high phosphorus levels, while getting infigratinib or these FGFR inhibitors, that these patients actually have potentially a higher response rate as well. So I think that has to be proven more in these bigger trials, but it's an interesting biomarker potentially for patients who might have good responses.

Dr. Gilligan: So for patients who had urothelial cancer resected or at high risk for relapse, this is an exciting new option for them, if they have the right genomic composition of the cancer and would not otherwise receive chemotherapy. So thank you for the summary.

Okay. So now we're going to talk about kidney cancer and the CYTOSHRINK discussion. [SBRT With Combination Ipilimumab/Nivolumab for Metastatic Kidney Cancer (CYTOSHRINK)] And we have Dr. Brian Shuch with us to discuss that. Brian, can we start off with who this study is designed for?

Dr. Shuch: It's really designed for patients with metastatic kidney cancer. Could be any type of kidney cancer, presenting with metastatic disease. We call that de novo metastatic disease. So they would have their primary tumor still in place in their kidney, with disease outside of that organ in other locations.

Dr. Gilligan: So these are patients with-- they have the tumor in their kidney, it's spread somewhere else, and they haven't had any other treatment so far? They haven't had any surgery or any drugs?

Dr. Shuch: Correct. These will be patients that are treatment-naïve that are going to start on their first course of treatment, which, in general, would be a discussion of either surgery or systemic therapy.

Dr. Gilligan: So at this point in time, what's the standard of care for such patients?

Dr. Shuch: We used to take every patient to surgery upfront. We call that a cytoreductive nephrectomy. Since we've had much better agents in recent years, and these agents have a lot of activity, we've done less upfront surgery as it appears that some patients may not benefit from racing off to the OR. So these are patients that generally would get started on systemic therapy first because this population, and this trial, has some risk factors for worse disease. We call that intermediate- or poor-risk features.

Dr. Gilligan: So these are patients who we would not normally do surgery on because it doesn't seem to help them, unlike some of the other patients who we do, the good-risk patients.

Dr. Shuch: Well, we are investigating that in other trials, but there are plenty of patients who are not going to run right to surgery, and these are the ones that we would consider deferring surgical management of the primary tumor. We would get started on systemic therapy, and we would reassess how they would be [treated] in the future, whether surgery was an option. But there are emerging entities such as radiation, which we'll discuss, which could be another exciting approach.

Dr. Gilligan: So if a patient that was going to go on this trial didn't go on the trial, they would most likely be treated with medications at this point in time. Is that correct?

Dr. Shuch: Correct. There'd be standard medications which are available off clinical trial which are right now dual therapy with 2 immune agents, or an immune agent and a tyrosine kinase inhibitor. So these are standard drugs that are available off a trial. Patients get started on therapy, and we see how they do later for other treatment options.

Dr. Gilligan: So what is this study looking at? What's the new thing that it's introducing and the question that it's asking?

Dr. Shuch: So kidney cancer, 10, 15 years ago, there was never really any role for radiation except for very rare circumstances. But now we have newer types of radiation where we're doing radiation at much higher doses in shorter time periods, and we call that ablative dosing. And as we've used that in brain and bone lesions for kidney tumors, and with excellent efficacy, with great—what we call local control. That has been applied to the primary tumor as well, and that's been used in many fields, that type of alternative radiation approach. We call that stereotactic radiation or the term radiosurgery, which is really a misnomer. It's just high dose ablative radiation, and it can be used in the primary tumor as a way maybe to kill the tumor.

Dr. Gilligan: And what is that outcome that we're hoping for? How would success be measured if this trial is positive?

Dr. Shuch: Well, we do know for small tumors, it seems to be a fairly effective measure at stopping tumors from growing. In this situation, it's employed after initiation of systemic therapy. Half the patients will get this radiation therapy to that primary kidney tumor, and the goal is to see if it delays progression of the disease. What we call progression is generally growth of lesions that are existing, or development of new lesions, new spots around the body. So the goal is to see if radiation with the standard immune therapy would delay progression versus the standard immune therapy alone.

Dr. Gilligan: So just to reiterate then, I guess for patients who are on this trial, normally they would get treated just with the immunotherapy or combined immunotherapy and targeted therapy, and what we're asking here is, if we give them radiation too, do they do better? Do we delay progression of disease? That we keep things under control longer, that they live longer?

Dr. Shuch: Correct. Obviously, living longer is a major factor. That's another objective of the study, but the study doesn't have enough patients or enough power to kind of detect that. The real issue is, does it delay the progression? And progression is important because if you have progression, often patients will progress to another line of therapy, meaning disease is not under good control.

Dr. Gilligan: Are there any known risks from the radiation therapy the patient should be aware of?

Dr. Shuch: Depending on the size of the tumor and the location to other organs, radiation could have some local effects. Obviously, there's some potential damage to surrounding structures such as the skin. There's some radiation that potentially could stray into other surrounding organs like the duodenum on the right side or the liver, the colon, small bowel, the ureter. And those organs generally can have some degree of toxicity. Generally, it's self-limiting with minor long-term effects, but we haven't done this for many, many years because it's a newer emerging modality. We do believe it's safe with large studies of smaller tumors, but patients do need to be aware that there could be some local irritation from radiation.

Dr. Gilligan: Is this trial still open to patients?

Dr. Shuch: So this is a trial based out of Canada by 1 of their cooperative groups in Ontario. It's a small study - only 78 patients - that opened this year. In discussion with the investigators, this study is accruing well, but it is anticipated to be open for another year. Because they're looking at what's called progression-free survival, we're hoping we can have results of this study within the next 2 years. Obviously, it is something open only to Canadian residents right now, but I will tell you that there are other groups in the U.S. that are considering similar types of trials in the Cooperative Group Network.

Dr. Gilligan: There's 1 final point I wanted to give you an opportunity to clarify for our listeners who may not be familiar with the idea of cytoreductive nephrectomy or cytoreductive treatment. So this is a treatment where we are targeting the primary tumor, even though there's other cancer elsewhere in the body that we can't remove. Can you just talk a little bit about the rationale for that, and why we're doing that?

Dr. Shuch: Historically in kidney cancer, when we had no effective therapy, we would have this phenomena: we removed the big bulky tumor, and 1% to 2% of patients would have their distant sites shrink, okay? And whether that was related to an immunologic phenomenon, maybe the tumor was secreting something, or maybe it was just overwhelming the body's defense mechanisms because they had a big tumor making them sick, it was kind of unclear. But we did know in larger trials with immune therapy, when we gave immune therapy in the old days, the agents like interferon-alpha or IL-2, we gave these agents, the primary tumor wouldn't shrink. Sometimes the distant sites could shrink, but it would not lead to what we call complete responses. So anyone who wanted to have a home run therapy where it was hoping to cure them, they would have their primary tumor removed first, and then they would potentially have the systemic immunotherapy. We've done 2 trials which showed, early in the 90s, that if you were able to remove the primary tumor and treat with these older immune agents, patients would have better outcome. And as those agents were pretty ineffective, we thought the survival benefit was really due to removing the big bulky primary. So the rationale for this trial is, you're not removing the big bulky primary tumor, you're potentially killing it with radiation, so you're overall reducing the burden of disease. There are some theoretical benefits of radiation where you kill tumors, and the tumors release what we call antigens. Basically, I try to explain that to people it's basically like a patch. Like a Boy Scout or Girl Scout has a new patch on them, and you'd recognize them as maybe having a badge of like hunting. So the tumor potentially might expose some of these bad patches, and the immune system might wake up and recognize them, and hopefully, then attack other sites of disease. So, again, the goal is either you're reducing the overall burden of disease in the body, or you're maybe allowing the body's immune system to kick in because you're killing a [tumor] there. We're just not sure really the mechanism, but it's been long used in kidney cancer, this idea of reducing the burden of disease.

Dr. Gilligan: Thank you for listening to this podcast. There are many different clinical trials currently enrolling people with genitourinary cancers. If you're wondering whether participating in a clinical trial might be right for you, please talk to your health care team.

ASCO: Thank you, Drs. Gilligan, Agarwal, Zhang, and Shuch.

Visit www.cancer.net/clinicaltrials to learn more about participating in clinical trials. All treatments have side effects—please talk to your health care team about possible side effects to watch out for.

And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough 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. 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 the data described here may change as research progresses.

Cancer does not affect all people equally. Some groups of people, including racial and ethnic minorities, poor people, sexual and gender minorities (LGBT+ people), adolescent and young adult populations, and older adults, are more likely to be diagnosed with cancer, or have poorer outcomes.

This is known as "health disparities." In today's podcast, Dr. Petros Grivas and Dr. Edith Mitchell discuss health disparities in cancer clinical trials, why it is important for clinical trials to be inclusive, and resources for people with cancer who face barriers to care.

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

Dr. Mitchell is Clinical Professor of Medicine and Medical Oncology at Jefferson Medical College of Thomas Jefferson University, and the Director of the Center to Eliminate Cancer Disparities at the Sidney Kimmel Cancer Center at Thomas Jefferson University.

View disclosures for Dr. Grivas and Dr. Mitchell at Cancer.Net.

ASCO would like to thank Dr. Grivas and Dr. Mitchell for discussing this topic.

Dr. Grivas: Hello. This is Petros Grivas. I'm a medical oncologist at Seattle Cancer Care Alliance. I'm an associate professor at University of Washington and associate member of the Fred Hutchinson Cancer Research Center. I'm real delighted today to be able to discuss with a legend in the field, Prof. Dr. Edith Mitchell. Dr. Mitchell is well-known internationally for her work in oncology as well as health care disparities. Dr. Mitchell is directing the Diversity Services features of the Sidney Kimmel Comprehensive Cancer Center, and is a full Professor there, she is a medical oncologist, as I mentioned. And in addition to many achievements that she has over the years, and her international role in cancer research education and patient care, a few examples of her achievements include that she has been selected to be a member of the President's Cancer Panel and also in the NIH Council of Councils, which speaks highly of her contributions in the field. And I was impressed to find out recently that she was the first woman physician that was promoted to the rank of general in the U.S. Air Force. And again, there're many other accomplishments. Dr. Mitchell and myself have no relevant disclosures in relation to this particular topic that we're discussing today. Dr. Mitchell, thanks for joining us today.

Dr. Mitchell: Well, thank you so much, Dr. Grivas. It's really good to speak with you again, Dr. Grivas. And thank you so much for the opportunity to discuss disparities with you today.

Dr. Grivas: Absolutely. And thank you so much, Dr. Mitchell, for your nice words. We talked a bit about health care disparities. And your work in the field is really, really important. Could you comment a little bit about health care disparities—the definition—and what we mean when we talk about that?

Dr. Mitchell: Sure. So when we speak about disparities, it's very important that we understand that for any disease process, whether it's a cancer disease or some other disease, if there are differences among communities, either in the incidence rates, that is, how often the disease or the problem occurs, as well as how often there are deaths. So mortality rates being different in different individuals. Could be men versus women, or Blacks versus Caucasians, or Latinx or other racial or ethnic, or differences even between the South and the North. There are a number of disparities that are different and occur more frequently in individuals who live in the southern part of the country. So disparities meaning that there are differences either in the number of occurrences or incidence rates or in the number of deaths, mortality rates, in different communities and among either a racial or ethnic groups or among people. For example, young patients versus older patients. So evaluating differences that occur among people because of their community.

Dr. Grivas: Thank you, Dr. Mitchell. This is very, very helpful to understand. You mentioned some very good examples. Can you elaborate a little bit further about who are the most negatively affected by this, in your opinion?

Dr. Mitchell: So it's well-recognized that men have higher death rates from certain cancers. It's also recognized that for the number of individuals that we've collected information about over the years, that African Americans have higher incidence rates of certain cancers and higher mortality rates of others. It's also recognized that African American men have the highest death rates and highest cancer occurrence rates or incidence rates of any group in the United States. So there are a lot of research ongoing now, evaluating men, and particularly African American men, to find out why there is a higher incidence rate and a higher death or mortality rate in this country. So lots of research.

There is also a lot of information that over many years, cancer incidence rates have been higher in Blacks compared to whites among males and in whites compared to Blacks among females. So while Caucasian women have higher incidence rates, the African American women have higher death or mortality rates. Also, we have evaluated cancer mortality rates in many different populations and it's still the fact that African American men as well as African American women have higher mortality rates compared to whites. So very important that research continues with those.

And for a few cancers, for example, prostate cancer in men, African American men have higher incidence rates of prostate cancer as well as higher death rates. Breast cancer, another area. African American women have higher death rates from breast cancer, although the incidence rates are approximately equal. African American women have more aggressive tumors and more of triple-negative tumors. And triple-negative breast cancer tumors are more aggressive tumors. They spread more rapidly, there are fewer medications to treat the cancers with, and consequently, overall death rate's higher in Black women compared to Caucasian women. Colorectal cancer, another where there are higher incidence rates, with African Americans having a 20% higher incidence rate of colorectal cancer in this country and African Americans having a 40% higher mortality or death rate in this country from colorectal cancer.

And then the last that I will mention-- now, I could go on and on with different cancers, but multiple myeloma. Multiple myeloma is probably the most disparate cancer of all of those in the United States. The incidence rate of myeloma in African Americans is twice that of Caucasian patients, and the death rate being even higher than twice as many. So there are so many different-- and consequently, it's important for clinical trials for us to-- understand everything from the preventive strategies and trying to prevent cancer in various populations through early detection and trying to find the cancers at an earlier stage. And the earlier we find the cancer, the better the treatment outcomes and better opportunities for a cancer cure. So really important.

And then, of course, there're the diagnostic studies. Treatments can be different in patients and consequently, finding the right treatment for the right patient at the right time being important. Also, we do research and clinical trials regarding posttreatment, quality of care, and survivorship. So really important for individuals to participate in clinical trials so that the patient can have access to and the opportunity to receive the latest information on treatment for this specific cancer as well as follow-up diagnostic studies, the specific scans, or other markers.

There, actually, Dr. Grivas, is a study ongoing where individuals may participate in a study even before they develop cancers or chronic diseases. And that's called the All of Us study. With All of Us, it is planned that approximately 1 million participants will be invited to participate in this trial, and information regarding a specific participant or a specific individual can be given back to the patient or the individual. Like I said, many individuals will not have developed a cancer or a chronic disease. And this might help individuals determine what the risk factors are for developing certain tumors over a period of time. So All of Us is another study by the NIH that will help determine risk factors for patients. So I think for every patient to try and find out information, 1, regarding the tumor if they have developed a cancer but, 2, determine screening strategies to try and find the tumor at an earlier stage and then opportunities for participation in prevention trials to try and prevent cancers from forming. So lots of different clinical trials ongoing and very important for specific populations.

It's well-recognized that African Americans have higher incidence and mortality rates. Latinx or Hispanic patients, there are some tumors that have higher incidence or higher death rates. And the Native Americans also, for certain tumors, have higher incidence rates and higher death rates. So so much in terms of clinical trials ongoing and especially for minority populations. Finding out information about a clinical trial and the opportunity for participating in a clinical trial, very important.

Dr. Grivas: These are excellent points, Dr. Mitchell. I want to ask you to comment a little bit on the efforts overall and your role in National Cancer Institute and other forums. What is the oncology community's trying to do to reduce these disparities? You mentioned clinical trials as a main important topic. But what resources are available to the patients in order to try to avoid those barriers and enroll in clinical trials and eliminate disparities in patient care?

Dr. Mitchell: Certainly. And that's a great question because individuals can, if there is access to the internet, go into clinicaltrials.gov. One can find information about trials as well as potentials for treatment trials and just basic information about the disease process. So if there is breast cancer, you can type in "breast cancer," and you'll get the information on breast cancer or any specific cancer. And I urge patients not to just go to the internet and look for things but go to the NIH or the NCI websites. Those are the areas where the greatest research has occurred, and this is research that is specifically targeted for the United States population. So we do provide that information. We also provide information that patients can give to their physicians and ask questions. Always ask questions to your physicians or other clinical staff. The nurses are great resources of clinical information. It's always good to ask those questions.

And if you use the internet, go to clinicaltrials.gov, and you will get the latest in terms of the National Cancer Institute studies. But you can also get information regarding the disease processes. And another good site is that of the American Cancer Society, which also has outstanding patient information that is reliable and trustworthy. So I usually recommend those 2 sites, but there are others. And especially if there is a National Cancer Institute-designated cancer center in the area. These are funded by the Congress and therefore are excellent areas for information as well as treatment. So I do recommend that patients utilize these resources instead of routinely just clicking on the disease process and seeing whatever comes up on the internet. There are some resources on the internet that are not reliable, that are not clinical trials, and I advise patients to be careful about obtaining information on the internet, and make sure it's from a trustworthy resource.

Dr. Grivas: These are great points, Dr. Mitchell. I appreciate all your work you have done in the field. That's one of the very valuable points for our audience today. I think the take-home message is for our patients and audience participants to ask questions, seek opportunities, make sure they discuss with their treatment providers about clinical trial opportunities for them to be involved in the research and clinical trials. As you mentioned, that's the way to move forward as well as to eliminate disparities in health care. So thank you so much again for your time today and your so-important insights for our audience. Thank you, Dr. Mitchell.

Dr. Mitchell: Oh, thank you so much, Dr. Grivas, and we look forward to working with you on the various projects that we have. And the last thing I'd like to say for patients, that despite the COVID-19 pandemic and the number of patients affected, if 1 has symptoms, then they should still discuss this with their clinicians and go in for cancer screenings, go in for cancer treatment. And if there are questions, talk with your physicians about it. Because although the coronavirus is here, cancer doesn't go away. So we still have to address cancer despite the COVID-19 pandemic, which affects so many Americans. But cancer is not going away. So still talk with your doctors about cancer screening and cancer treatment. Thank you.

Dr. Grivas: Fully agree with you. Great point. Absolutely. And thank you for pointing this out to avoid delays in cancer diagnosis, avoid delays in screening and proper workup. Thank you so much, Dr. Mitchell, for your time today.

ASCO: Thank you, Dr. Grivas and Dr. Mitchell. Learn more about cancer disparities at www.cancer.net/disparities. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough 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. 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 the data described here may change as research progresses.

In this podcast, Dr. William Dale will discuss new research presented at the International Society of Geriatric Oncology 2020 Annual Meeting, held virtually on October 1st.

Dr. Dale is director of the Center for Cancer and Aging Research at City of Hope, a comprehensive cancer center near Los Angeles. He is also the Cancer.Net Associate Editor for Geriatric Oncology. View Dr. Dale's disclosures at Cancer.Net.

ASCO would like to thank Dr. Dale for discussing this topic.

Dr. Dale: Hello. Welcome to Cancer.Net. Today, I'm going to discuss research highlights presented at the 2020 International Society of Geriatric Oncology, or SIOG, Annual Meeting. I'll be discussing 2 kinds of studies. One, the rapid-fire abstracts, which were the featured abstracts in this year's virtual meeting of SIOG. And at the end, a practice-changing article that was presented. I don't have any disclosures for the rapid-fire abstracts. However, the article that was chosen for hematology to be the most relevant and practice changing this year is 1 in which I participate as a coauthor. But the majority of the work was done by others. And I will describe it when we get to that point in the discussion. So let's jump right in.

The first study is the qualitative study of a mobile health exercise intervention focused on older adults with myeloid neoplasms. So in this study, a specific intervention from the University of Rochester, a home-based exercise program referred to as GO-EXCAP was applied to older adults to help prevent the decline of physical function and side effects, primarily fatigue, in patients with multiple myeloma. This is a mobile health application which is done in the home and is largely a qualitative study with people over the age of 60. The primary findings were that this intervention was found to be especially helpful for these patients over 60. It was easily applied in the home and could be used for 5 to 30 minutes 2 to 4 times per week. Patients were starting it at the beginning of their chemotherapy. They especially liked the instructions that were provided. Found it very easy to apply and were able to engage with their family and family members during the course of using this intervention. It does involve a web portal and requires a mobile device, so people need to have those. But the activity tracker that was used, which is a common one, was provided by the team. It looks like a very promising potential intervention, knowing how important exercise is, with some caveats on the use of technology for older patients.

Another study, a second study, is on the feasibility of doing a pragmatic geriatric assessment in a low-resource country, which is Brazil. So the goal of this study was not just to apply the geriatric assessment, which is known to be of importance for any older adult 65 and above with cancer, but to make it very practical and for use in an environment where you don't have all the resources you would have in an academic setting. So prior to an initial consultation, a nurse would apply the pragmatic geriatric assessment that included some very straightforward tests, ones that are recommended through the ASCO guidelines in 2018 and the SIOG guidelines that just came out. This was gait, speed test, a four-meter walk, a polypharmacy questionnaire, a mini nutritional assessment, a geriatric depression scale with 5 questions, and a mini COG, which is a small cognitive assessment for a few moments. They did this in a population of patients whose average age was 73 years old with a range from 61 to 93. And a number of findings. 39% of people were fit, but 22% were frail. With the rest, about 40%, in the prefrail state. A large majority, over 50%, were experiencing polypharmacy. 23% had depression. And 42% had concerns about cognitive impairments. We are able to show that even in a low-resource environment where it's typically difficult to apply a geriatric assessment this pragmatic assessment was able to be conducted, completed, and the major domains of a geriatric assessment were instigated. Significant numbers of deficits were found suggesting that interventions for these would be appropriately intervened on. And that would be the next step, is to show that we can use the known interventions to decrease the rates of these concerns.

The next abstract is 1 on the prevalence of geriatric syndromes in community-dwelling older adults. Geriatric syndromes are a common collection of concerns that older adults develop that cluster together and that tend not to happen in younger individuals. A good example is functional impairments, where the inability to do activities around the home is not possible for older adults. Falls is another common one, where multiple contributing causes lead to people falling a common outcome. Also, cognitive impairments among older adults is another geriatric syndrome. Again, this is an international study in Japan in which over 2,000 people over the age 65 and an average age of 72 were investigated for the prevalence of geriatric syndromes. A number of validated tests were applied to this group of patients and logistic regression was used to find those aspects that were most closely identified with having geriatric syndromes. Over 200 patients, about 10%, had a history of cancer. The prevalence of various outcomes, including physical impairments, depression, and kidney dysfunction, ranged from 4% up to 22%. In particular, the associations of physical impairments was about twofold higher in predicting the presence of a geriatric syndrome. And the community-dwelling older patient survivors had a high prevalence of these syndromes compared to elderly individuals without cancer, making the presence of cancer a concerning marker for the development of geriatric syndromes, even after cancer treatment when people are survivors.

And my last abstract of note was the use of extreme hypofractionation in stereotactic body radiation therapy in older patients with prostate cancer. So 179 patients over the age of 70 who were treated with radiation therapy for clinically localized prostate cancer had the EPIC-26 questionnaire which assesses a range of outcomes at multiple intervals over the next few months to years. And it was found that this extreme hypofractionation, or SBRT, stereotactic body radiation therapy, was very well tolerated in this older adult population with minimal numbers of side effects and led to excellent disease control over the first 3 years of treatment, making it a very well-tolerated and potentially best option for older adults with localized prostate cancer, especially those who have other comorbidities, other geriatric syndromes, and for whom disease control is appropriate. So those were the most important abstracts at the conference.

Next I'm going to move to a hematology study that was cited as the most important and potentially practice-changing published in Blood Advances by lead author Benjamin Derman and senior author Andrew Artz. In this study, a multidisciplinary clinic, guided by geriatric assessments, was used to optimize the care for older adults who are being considered for a hematologic bone marrow transplantation. Patients over 60 years old at a clinic at the University of Chicago had an evaluation of their candidacy for transplantation and then optimization of their care prior to and throughout the transplant process. This multidisciplinary assessment and optimization was conducted through patient surveys, on-site function and cognitive assessments, nutrition optimization, along with the participation of a multidisciplinary team that included PT and OT, a geriatric oncologist, the transplant physician, nutrition, infectious diseases, social work, and then a team discussion following a day evaluation.

This led to important improvements in transplant outcomes. And these outcomes improved over time, likely through a combination of better decision making about who receives the transplantation, those who are most fit going forth. And those who are most frail, perhaps offered other treatment options. This led to decreased deaths during an inpatient stay of transplantation, decreased nursing home admissions, decreased nonrelapse mortality, and increased survival, along with increased quality of life. This approach to older patients, who are now being increasingly considered for transplantation, does await formal randomized controlled trials to prove this approach is right. This was an observational trial but had quite a few patients and would indicate the value of having geriatric assessment-guided multidisciplinary team interventions.

So there's many other presentations and summaries in various fields at SIOG this year in both solid tumors and hematology, along with geriatrics in general. Please go to the SIOG 2020 website to get all the details and to read about more details from the abstract presentations and to see the presenters on the recordings. Thank you very much. And I look forward to seeing you all online.

ASCO: Thank you, Dr. Dale. 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 on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough 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. 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 today's podcast, Dr. Paul Appelbaum, Dr. Allison Magnuson, and Dr. Jonathan Marron, will discuss their article "Medical Decision-Making in Oncology for Patients Lacking Capacity," from the 2020 ASCO Educational Book. They discuss what it means for someone to be unable to make significant medical decisions for themselves, known as "decisional capacity," and offer practical tips for families and caregivers.

Published annually, the Educational Book is a collection of articles written by ASCO Annual Meeting speakers and oncology experts. Each volume highlights the most compelling research and developments across the multidisciplinary fields of oncology.

Dr. Paul Appelbaum is a psychiatrist at Columbia University Medical Center, where he researches decisional capacity and decision-making in medical contexts. Dr. Allison Magnuson is a geriatric oncologist at the University of Rochester, where she researches older adults with cancer and older adults with preexisting cognitive impairments. Dr. Jonathan Marron is a pediatric oncologist, bioethicist, and researcher at the Dana-Farber Cancer Institute and Boston Children's Hospital.

View disclosures for Dr. Appelbaum, Dr. Magnuson, and Dr. Marron at Cancer.Net.

Dr. Marron: Hi. We wanted to welcome you to this Cancer.Net podcast. Today we're going to discuss our article in the 2020 ASCO Educational Book which is entitled "Medical Decision-Making in Oncology for Patients Lacking Capacity." What we hope to focus on today specifically is what this means for patients, for families, for caregivers, and provide some practical guidance not just for oncologists but for patients, families, and caregivers specifically. My name is Jonathan Marron. I am a pediatric oncologist, bioethicist, and researcher at the Dana-Farber Cancer Institute and Boston Children's Hospital.

Dr. Appelbaum: And I'm Paul Appelbaum. I'm a psychiatrist at Columbia University Medical Center where I do research on, among other things, decisional capacity and decision making in medical contexts.

Dr. Magnuson: And I'm Allison Magnuson. I'm a geriatric oncologist at the University of Rochester, and my research focuses in older adults with cancer and more specifically in older adults with preexisting cognitive impairments.

Dr. Marron: We should point out that none of the 3 of us have any relevant conflicts to disclose. Dr. Applebaum, can you tell us a little bit about what capacity is and why it matters to patients and their families?

Dr. Appelbaum: So capacity is both an ethical concept and a legal construct. And it refers to those decision-making abilities that we require people to have, in order to make decisions that are binding decisions, valid and worthy of respect by others. Over the years, this notion of decisional capacity has evolved in a more focused way. So it was once the case that people were considered to be capable of making all decisions or no decisions. And now we recognize that people may be capable of making some decisions but not others. Moreover, we recognize that this capacity taken as a whole can change over time. So if you're sick, in pain, anxious, or of course unconscious, you may lack capacity to make decisions at that point. But the following day, when you are feeling better, no longer in pain, or have consciousness, you'll be quite capable of doing it for yourself.

And then we focus in on 4 components of capacity which is what we look to assess when somebody is concerned that a patient may lack capacity. We ask whether the person can understand the information that's relevant to the decision, can appreciate what that information means for their decision-making context, can reason about the decision in a more or less rational way, and can make a choice and decide whether or not they want a particular treatment or want to be hospitalized or desire a diagnostic procedure. So in a nutshell, that's what we mean by this thing that we call decisional capacity.

Dr. Marron: And so you just mentioned there a couple of different types of decisions that an individual might have to make. Might capacity vary according to each individual decision?

Dr. Appelbaum: Yeah. But capacity is usually thought of as task-specific. So that even within the domain of medical decisions, a very simple decision like should you have a flu shot, like I did last week, is probably not one that requires a great deal of capacity. Indeed, they didn't give me any hard time when I asked for a flu shot. But if you're making a decision that has potentially life-saving or life-changing consequences, whether to accept, for example, or reject potentially life-saving treatment, more capacity may be required. So it depends on the decision that's at hand.

Dr. Marron: So it sounds like as it relates to decisions that an individual with cancer might face, or those who care for individuals with cancer, this could end up being a relatively challenging process. Dr. Magnuson, what are some of the aspects of cancer and cancer care that might affect an individual's ability to have capacity for these kinds of decisions?

Dr. Magnuson: Sure. I think that's a great question. So as Dr. Appelbaum mentioned, certainly the complexity of the decision can come into play. We know that with cancer treatment, some of the treatments that we consider are high risk types of therapies, potentially high benefit but also high risk. And if patients have some type of preexisting cognitive impairment, perhaps some of those more complex decisions may be more challenging and require more support. There are also scenarios with a cancer diagnosis, for example brain metastases, that may impact capacity for certain patients as well.

Dr. Marron: And then back to Dr. Applebaum. So if there's questions about whether or not an individual has capacity, what should patients and family members expect that their clinicians will do in order to assess that?

Dr. Appelbaum: Yeah. I think it's important to say, first of all, that if family members believe that their loved ones may lack capacity, and sometimes they know much better than a doctor or any other member of the medical team who has just met the patient what their baseline functioning is and how different they may look and behave today, that if they suspect that that's something that they ought to communicate to the medical team. If that happens or if the team itself suspects that the person may have some impairment of their decision-making abilities, an assessment will take place. It can be performed by some member of the medical team itself or sometimes it will be done by a consultant. Typically, a consulting psychiatrist who's called in to see the patient and do the evaluation. Unlike blood tests for anemia, let's say, there's no definitive medical test that can be done to determine whether somebody is decisional and capable or not.

The assessment is based on an interview. The interview typically will review what the patient understands about their condition and its nature, the treatment that's been proposed, the risks and benefits, and the alternatives along with their risks and benefits. It will assess whether the patient appreciates their own situation, that is recognizes the nature of their illness and its severity and what the likely consequences of either accepting treatment or refusing treatment might be. It will assess their ability to weigh the risks and benefits and come out with a decision. Typically, a decision that in some way reflects their assessment of those risks and benefits. That sort of interview can take 20 to 30 minutes. It's done at the bedside and the person doing it will integrate that information with information from the family if that's available with a review of the medical chart to see what other problems the person may be having or what variant behaviors or thoughts they may have manifested and will come up with a conclusion.

What's important to underscore as we mentioned earlier is that conclusion is valid for that point in time. If the patient's condition changes, somebody who was competent yesterday may not be today and somebody who lacked that competence yesterday may have recovered it by today, and again if family members are aware of substantial changes in their loved one's condition, that's important to call to the team's attention as well.

Dr. Marron: And that last point that you mention is particularly poignant in my area of practice in pediatrics, since children by definition legally don't have capacity. So we have to think about things in a little bit of a different fashion where typically the child's parents are the ones who are tasked with making decisions on behalf of the child. But we try to integrate the child's voice as best that we can and the age and developmentally appropriate way while understanding that until the age of majority, in most cases an individual doesn't have the legal ability to make a decision for themselves.

That's not to say, however, that just because they can't make a legal decision doesn't mean that they shouldn't have a voice. In your practice, Dr. Magnuson, how do you try to approach patients that don't have capacity or have perhaps waxing and waning capacity?

Dr. Magnuson: Yeah. It's interesting kind of hearing your pediatrics perspective. Because of the area of my interest, many of my patients do come to see me with a new cancer diagnosis and they have preexisting either mild cognitive impairment or dementia. And just as we've been talking about how the complexity of the decision at hand really is an important thing to consider. Often patients may retain the capacity for some of the more straightforward decisions but may need more involvement of caregivers, health care proxy, and such for the more complex, maybe treatment-focused decisions. Thinking through different options, cancer treatment options that have different risk profiles to them. Those are complex decisions and so often how I try to approach it is to really get a sense from patients, as Dr. Applebaum described, what is their understanding about their diagnosis?

Some patients with advanced cognitive impairment may not recall that they have cancer even though they've been to several appointments prior to me where the diagnosis has been discussed. Those are more extreme cases certainly, but kind of getting that level of understanding using a lot of interview techniques in the office visit to gauge people's understanding of the different options that we're talking about. What are the goals and preferences that they're coming to this decision with? Just to get a sense of how are they reasoning through these options and certainly engaging their family and their support. But really emphasizing that they may retain capacity for certain decisions. So we don't want to ignore as you said their voice and their input, even for those more complex decisions.

Often patients I'm seeing are older and they've had many life experiences that have informed their decisions, so their family does come with that knowledge. And so it's important to really kind of evaluate those aspects as well.

Dr. Marron: And with that in mind, is there any advice that you might give to a family member of a patient who will be coming in to the oncology clinic with the expectation that decisions you're going to have to be made, but that the patient him or herself is not thought to have capacity presently? How can families and caregivers help to prepare for meetings like that and decisions like those?

Dr. Magnuson: That's a great question. So sometimes I do see family struggle with kind of really wanting the patient to make the decision themselves. But they're just unable to kind of retain all the detailed information that would go into that decision. And I can see that sometimes be challenging for patients, especially if there's the level of cognitive impairment wasn't maybe previously appreciated to the degree that it's actually present. And so I definitely try to work with patients and families to kind of all be on the same page at kind of where that level of decisional support is needed and try to engage everyone together. I guess as far as advice. certainly as Dr. Appelbaum said, if there's concerns that you as a family member have in this regard sharing that with the team is always helpful and really kind of helps us to make sure that we're assessing at each point kind of that level of understanding.

Dr. Appelbaum: It's probably worth noting that in most cases, unless the patient him or herself has designated another decision maker, it will be the family that the treatment team will turn to to make decisions for an incapable patient. And one of the ways the family can prepare for that in advance is to try to ascertain as early as possible in the process what the patient's desires are, how aggressive they want to be about treatment, how they feel about issues like do not resuscitate orders and other choices that they may have to make, for example, with regard to palliative care or facilities where they may want to be if they get towards the end of their lives.

Dr. Magnuson: Yes, I agree with that Dr. Applebaum. Kind of that ongoing discussion with families about what people's goals and preferences are and they definitely evolve over time, too, I think. So kind of having that open dialogue is important.

Dr. Marron: Seems like a common theme here is how much this can change both for a given individual and then over time and according to different scenarios and different decisions. We certainly see that in the pediatric space as well as children get older and they move through the illness experience, they may develop a greater degree of ability to participate in decisions even if they're still under the age of majority and/or if they get sicker. As Dr. Magnuson mentioned, it's possible that any involvement they had may decrease over time.

Any other pieces of advice that either of you would want to provide to a friend, a family member or a patient who might be coming to clinic and be faced with some of these challenges?

Dr. Appelbaum: So family members are often uncomfortable with their role as decision makers. I know this from my own life, my own experience when I made decisions for my mother at the end of her life and it wasn't easy, and I still think about those choices. But there's general agreement among bioethicists today that the best way to think about these decisions is to try to ascertain what the patient would have done in that circumstance and rather than making a decision for the patient, see yourself as making the decision that the patient would have made if the patient were capable of doing that.

Now sometimes we just have no evidence of what the patient would have wanted, and we have to do the best we can and we make a choice in their best interests. But in so far as we can actually reflect desires, that I think is generally acknowledged to be preferable and is part of the point of those advance discussions that we were talking about a few minutes ago.

Dr. Marron: It's such an interesting and important point because I think that brings up one of the important distinctions in a practical fashion between adults and children and adolescents in this area because children don't have that sort of experience to show parents what they would want. So we have to work as a team to try to integrate both what we feel is in the best interest of the child but also in a way if we can integrating any values or preferences that we're able to elicit from the child or more often the adolescents when making decisions on their behalf.

Well, before we close are there any other additions that are giving you Dr. Appelbaum or you Dr. Magnuson would like to add?

Dr. Appelbaum: I think we've covered the points that [crosstalk] I wanted to make sure we did today [laughter].

Dr. Magnuson: Yes.

Dr. Marron: All right. Well, thank you both and thank you to everybody for joining us with this podcast. Okay. If you're interested in learning more about any of the things that we've talked about today you can visit ASCO.org/edbook. And there you can find the paper that we dive into this in a little bit more depth.

ASCO: Thank you, Dr. Appelbaum, Dr. Magnuson, and Dr. Marron. Please visit ASCO.org/edbook to read the full article. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough 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. 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 the data described here may change as research progresses.

In this podcast, Dr. Neeraj Agarwal discusses new research in kidney, prostate, and bladder cancer presented at the European Society for Medical Oncology Virtual Congress 2020. This meeting was held virtually September 19-21.

Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. He is also a Specialty Editor for Cancer.Net. View Dr. Agarwal's disclosures at Cancer.Net.

ASCO would like to thank Dr. Agarwal for discussing this topic.

Dr. Agarwal: Hi, my name is Dr. Neeraj Agarwal. I'm a professor of medicine and the director of genitourinary oncology program at the Huntsman Cancer Institute, Salt Lake City, University of Utah. Today, I'm going to talk about 3 major clinical trials which were presented during the 2020 annual meeting of European Society for Medical Oncology. All these 3 trials are practice-changing trials. And they have huge impact on how we treat patients with bladder cancer, prostate cancer, and advanced kidney cancer. Before I proceed further, I want to disclose that I have consulted and received honorarium to the sponsors of all these 3 trials, which include Exelixis, Galentic, AstraZeneca, Pfizer, and EMD Serono. I was also involved in the conduct of the PROfound clinical trial, the trial in prostate cancer which I am going to discuss about, as a steering committee member.

Let's start with the trial in advanced kidney cancer. So this trial was a large phase III trial. It was named as 9ER trial and used a novel combination of cabozantinib plus nivolumab versus sunitinib. Hundreds of patients were randomized to treatment with cabozantinib plus nivolumab versus sunitinib. What we saw was really remarkable. The progression-free survival, which is defined as how long these drugs were able to control the disease from progressing, was remarkably improved with the combination of cabozantinib plus nivolumab versus or over sunitinib. In fact, the progression-free survival was double with the novel combination of cabozantinib with nivolumab versus sunitinib. So if you look at the absolute months, how long the disease was controlled or was contained from progressing, it was 16.6 months with the novel therapy with cabozantinib and nivolumab versus 8 months with sunitinib. In fact, if you look at the progression-free survival estimate as assessed by the treating clinicians who were treating these patients, it was even higher at 19 month versus 9 month.

Overall survival was also improved. We do not have data in absolute months in overall survival, but if you look at the hazard ratios, basically that means that there was a 40% reduction in risk of death on treatment with cabozantinib and nivolumab. Even response rates were twice as high with cabozantinib and nivolumab. The most important aspect I would like to highlight of this trial was the quality of life as reported by the patients. The health-related quality of life in patients who received cabozantinib with nivolumab was consistently better throughout the duration of trial treatment over those patients who received sunitinib. And this speaks of the overall tolerability and safety of the agent. To summarize, the combination of cabozantinib and nivolumab is one of the new standard of care options for our patients and improves survival and quality of life in a very meaningful fashion. Thank you very much for listening to the data of the 9ER trial.

Now I will move on to the prostate cancer trial. The name of the trial in prostate cancer was the PROfound trial. I'd like to bring to your attention that this is the first-ever phase III or large randomized trial which was successful, which was positive, in the realm of metastatic or advanced prostate cancer, where patients were selected based on a biomarker. The biomarker in this context was mutation in the DNA repair gene inside the cancer cells. So truly, it was a very novel trial, with a novel design, and a really new idea in the field of prostate cancer.

So in this trial, around 400 prostate cancer patients or patients with advanced prostate cancer, who were experiencing disease progression on novel hormonal therapy such as abiraterone or enzalutamide, and they could have received chemotherapy as well, were randomized to treatment with olaparib, a PARP inhibitor which targets those cells which harbor the DNA repair mutations or DNA repair gene mutations. So patients were randomized to treatment with either olaparib or the other novel hormonal therapy which they had not received before, which were enzalutamide or abiraterone. The patients were divided into 2 different cohorts. The first cohort had patients with BRCA1, BRCA2, and ATM gene mutations. The second cohort included patients with 12 other different types of mutations, also in the DNA repair gene. Again, what we saw was really striking. Treatment with olaparib resulted in delaying of disease progression as well as a significant increase in the overall survival. Overall survival was improved in these patients by almost 4 and half months on treatment with olaparib. If we look at the median overall survival in patients who did not get olaparib and who were on enzalutamide or abiraterone, the median overall survival was 14 and a half months. And that had improved by almost 5 months in patients who received olaparib. It basically translates into 30% reduction in risk of death.

I would like to bring to your attention, is that almost two-thirds of patients on this trial who received abiraterone or enzalutamide were allowed to cross over to novel therapy with olaparib during the conduct of the trial when they had disease progression on enzalutamide or abiraterone. So when you factor in this crossover— because whenever you see crossover, it always leads to attenuation or a decrease or apparent diminution of the survival benefit. If you account for the crossover of those two-thirds patients from control arm to the olaparib arm, the median overall survival was even further improved with almost a 60% reduction in risk of death. The side effects with olaparib— there are 2 main side effects which I would like to mention. One is nausea, and 1 is anemia, which really differentiated olaparib from the alternative enzalutamide or abiraterone. And these 2 side effects are easily manageable in the clinic. So based on these data, olaparib was approved by FDA and now is available in the clinic.

I think the biggest challenge for us is to identify those patients who are candidates for treatment with olaparib. So any time a patient sees a doctor, a patient with advanced prostate cancer sees a doctor, it is extremely important that the discussion about genomic testing is brought up. Genomic testing of the tumor, genomic testing of the tumor tissue, as well as the circulating tumor DNA coming from the tumor, which is floating in the bloodstream, and referral to a germline testing clinic. Because many of these mutations are heritable and they can result in familial predisposition of other cancers.

So, to summarize, PROfound trial in advanced prostate cancer patients for the first time showed that patients can be selected for a targeted therapy based on underlying mutation in the DNA repair gene in their prostate cancer cells. And if they have these mutations, they are candidates for treatment with olaparib. There's another drug which also got approved in a very similar setting in patients who have already received chemotherapy, is rucaparib. So there are 2 drugs now which are approved in this setting for the patients who are harboring these DNA repair gene-related mutations.

So the final message which comes from the PROfound trial is a very important one. Every patient with advanced prostate cancer has to be tested for the presence of these mutations in their DNA repair genes in their tumors. And this mutation testing can be done by testing of the tumor tissue or by a simple blood test which looks at the circulating tumor DNA coming from the tumor tissue which is floating in the bloodstream. And of course, all patients need referral to a high-risk genetics clinic to be assessed for the hereditary component of these mutations to make sure they're not carrying these mutations in their germline DNA, which may potentially result in hereditary or inheritable nature of this mutation.

Now I'd like to talk about the main trial which has already changed practice in patients with advanced or metastatic bladder cancer.

The name of the trial is JAVELIN Bladder 100 trial. The earlier data was presented in the 2020 Annual Meeting of American Society of Clinical Oncology. And more data was presented in 2020 Annual Meeting of European Society for Medical Oncology. In the JAVELIN Bladder 100 trial, hundreds of patients with advanced or metastatic bladder cancer, who were receiving treatment with first-line chemotherapy with cisplatin or carboplatin and had received at least 4 to 6 cycles of these chemotherapies and did not have any evidence of disease progression, so they could be responding or they could have had stable disease - they had to have stable or responding disease - were randomized to treatment with avelumab versus best supportive care, meaning they were just watched carefully by the doctors, which is the current standard of care. So these patients who have stable disease or responsive disease after 4 to 6 cycles of platinum-based chemotherapy, they're watched carefully. So this was done in this trial for those patients who were on the best supportive care arm. And half of the patients received--in addition to periodic scans, they received treatment with an immunotherapy known as avelumab.

Again, what we saw was really striking. The overall survival was clinically and significantly improved in patients who received avelumab. The improvement in overall survival with avelumab was approximately 7 months. So 14 months in patients who did not receive avelumab and 21 months in patients who received avelumab. This translates into 30% reduction in risk of death in those patients who received avelumab. Please note that the benefit with avelumab was present in every subset of patients in this trial. It didn't really matter where the disease was present, whether it was present in the viscera versus only lymph nodes, whether tumors were expressing a certain biomarker known as PD-L. Every group of patients responded to avelumab.

The side effects of avelumab are not new to the patient and physician community. This drug has been approved in the later lines of bladder cancer treatment for almost 2 years now. Most of the side effects which happen are really easily manageable. And in less than 3 to 4% of patients, side effects can be more severe. We call them grade 3 and 4 side effects. And basically, they manifest as diarrhea, skin rash, liver function abnormalities. And for these reasons, patients who are receiving avelumab, they need to be followed by their oncologist at least on a monthly basis.

Having said that, I think these data are wonderful news to our patients. In fact, we have never seen such magnitude of overall survival improvement in patients with advanced or metastatic bladder cancer in this setting ever. Thank you very much for listening to me regarding the data of the JAVELIN Bladder 100 trial.

ASCO: Thank you, Dr. Agarwal.

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 on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

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