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.

Every year, the ASCO Annual Meeting brings together attendees from around the globe to learn about the latest research in the treatment and care of people with cancer. This year, attendees from 138 countries worldwide gathered virtually for the ASCO20 Virtual Scientific Program, held Friday, May 29 through Sunday, May 31.

In the annual Research Round Up podcast series, Cancer.Net Associate Editors answer the question, "What was the most exciting or practice-changing research in your field presented at the ASCO20 Virtual Scientific Program?" In this final episode of 2020, editors discuss new research in the fields of central nervous system tumors and lymphoma.

First, Dr. Glenn Lesser will discuss new research on a form of non-Hodgkin lymphoma that begins in the central nervous system, and research into a possible treatment for breast cancer that has spread to the brain. Dr. Lesser is the Louise McMichael Miracle Professor and Associate Chief in the section on Hematology and Oncology in the Department of Internal Medicine at Wake Forest University, with joint appointments in the Departments of Anesthesiology, Neurosurgery, and Public Health Sciences. He is also the Cancer.Net Associate Editor for Central Nervous System Tumors.

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

Dr. Lesser: Hello. My name is Glenn Lesser, and I'm a professor of medical oncology and director of medical neuro-oncology at the Wake Forest Baptist Comprehensive Cancer Center in Winston-Salem, North Carolina. I'm also the editor of the brain tumor section for ASCO's Cancer.Net. And today, I would like to briefly discuss what I think are 2 of the most clinically relevant research studies on brain tumors that were presented at this year's ASCO's Virtual Scientific Program. I should say right up front I have no disclosures or relationships that are relevant to the particular studies I'll be discussing today.

Unlike the progress we've seen in the treatment of many cancers over the past few years, patients with brain tumors and the physicians who care for them have not seen the same rapid advance in effective treatment strategies. Cancer that begins in the brain, so-called primary brain tumors, and the more common situation of cancer that spreads to the brain after originating elsewhere in the body, so-called metastatic or secondary brain tumors, still have relatively few effective treatment options available. However, I believe that the 2 abstracts we'll discuss today may impact the way that we treat certain primary and metastatic brain tumors in the future.

The first study I'd like to talk about was presented by Dr. Omuro on behalf of a group of international colleagues that described a randomized study of standard chemotherapy with or without low dose whole brain radiation in patients with a brain tumor known as a primary central nervous system lymphoma, which I may also talk about as a PCNSL for abbreviation. Non-Hodgkin's lymphoma is a relatively common cancer that involves the blood and lymph nodes throughout the body. Primary central nervous system lymphoma is the term used when patients develop a non-Hodgkin's lymphoma that's confined to the central nervous system which is really made up of the brain, the spinal cord, the spinal nerves, and the spinal fluid. This turns out to be a pretty rare diagnosis with only about 1,500 new cases of this cancer occurring in this country each year. This type of lymphoma is important, though, because it's very treatable in most patients, and a significant percentage of our patients can be cured with appropriate therapy. Because the disease is so rare, we really don't have the results of large clinical trials to help us determine the best treatment approach for patients with primary central nervous system lymphoma. And as a result, there are a variety of controversies over how to initially treat patients who develop this lymphoma, so-called induction therapy, as well as what type of treatment to give once the disease has been made to go away, or so-called consolidation therapy. In the past, radiation therapy to the whole brain was used to treat patients with PCNSL. And most of these patients who were treated with radiation-containing regimens had their tumors respond, although the cancer frequently returned within a year or 2. This approach has really fallen out of favor over the last few decades because of the very high incidence of neurotoxicity or brain damage from the radiation that was seen in surviving patients.

Unfortunately, a significant number of those patients who were treated with high doses of whole-brain radiation therapy developed a progressive irreversible dementia over the years following the radiation treatments, and a particularly high incidence of this toxicity was seen in patients who are over the age of 50. With current multi-agent chemotherapy regimens, a high percentage of treated patients are having their lymphomas go away. Unfortunately, a significant number of patients still have their disease come back within months or years of this treatment. And so strategies to consolidate or lock in that initial good result with treatment are being evaluated. These strategies may involve high doses of different types of chemotherapies, consideration of bone marrow or stem cell transplant, and even long-term maintenance treatment with oral chemotherapies. More recently, low doses of whole-brain radiation therapy have been explored as a way to try to prevent these lymphomas from coming back with a thought that the low doses of radiation might have minimal long-term brain toxicity as compared to the high doses of radiation given in the past.

So this study that was presented at ASCO involved about 91 patients with primary central nervous system lymphoma. Half of them received the low-dose whole-brain radiation therapy after their tumors were treated with several months of multi-agent chemotherapy, while the other half did not get the radiation. After a follow-up period of 4 to 5 years, the results of this treatment were that the patients who received the low-dose radiation in addition to chemotherapy lived longer and had a significantly higher rate of their tumor going away and staying away at least at the 2-year follow-up tie point. Now, data is not yet available on the neurocognitive outcomes in both groups of patients. That is how well their brains were functioning with tasks like memory, calculations, and personality. The improved results seen in this group of patients who got radiation suggests that this approach may be one effective way of helping to consolidate the treatment of primary central nervous system lymphoma after the induction chemotherapy.

These results, however, can only really be fully interpreted and applied once we have more long-term information on whether the patients treated in this fashion suffer from the high rate of neurotoxicity and dementia that was seen in prior studies using the higher doses of radiation. With further follow-up, this study should provide us with some definitive information on whether the strategy of adding low-dose radiation following standard induction chemotherapy is a good one for patients with primary central nervous system lymphoma.

The second study I'd like to talk about was presented by Dr. Nancy Lin, again on behalf of an international group of colleagues, and described the results of a trial adding a new drug called tucatinib to a standard chemotherapy regimen of trastuzumab and capecitabine in women with HER2-positive breast cancer involving the brain. Now, many common cancers have a tendency to spread to the brain if they recur after initial treatment. This metastatic or secondary involvement of the brain occurs in over 200,000 patients a year in the U.S., and new treatments for brain metastases are desperately needed. Women with advanced breast cancer are particularly susceptible to developing brain metastases, particularly if they have the subtype of breast cancer known as HER2-positive disease. In HER2-positive disease is defined that way because of the presence of the HER2 protein on the surface of breast cancer cells. Although a number of effective treatments have been developed for patients with HER2-positive breast cancer involving the body, including some common drugs like trastuzumab and pertuzumab, these agents have not been particularly effective in either treating breast cancer that has spread to the brain or preventing the breast cancer from spreading to the brain in the first place.

One of the main reasons why these chemotherapy drugs have not been effective in treating breast cancer metastases in the brain is that unlike the other organs in our bodies, the blood vessels of the brain are formed in such a way that they carefully restrict what substances in the blood are able to leave the blood and spread into the brain. Normal blood vessels in our body are somewhat leaky. And fluids, proteins, drugs can leak out of those vessels into the tissue with some freedom. The blood vessels of the brain, however, are lined by cells that tightly joined together to create a blood-brain barrier that is not leaky, and that barrier protects the brain from compounds that are circulating in our bloodstream which could adversely affect brain function if they were able to get into the brain in any concentration. Because of this barrier, most of our standard chemotherapy and anticancer drugs simply cannot cross the barrier to reach the cancer cells within the brain. In part, because of this, patients whose cancer had spread to the brain have typically been excluded from most of the clinical trials evaluating new drugs and treatments for breast cancer. The study reported by Lin at ASCO tested the ability of a new HER2-targeted drug, tucatinib, which because of its chemical structure has good penetration across this blood-brain barrier. Earlier smaller studies had suggested that this drug did indeed get into the brain at concentrations that could effectively treat breast cancer involving the brain. In this study, almost 300 patients with metastatic breast cancer involving the brain were treated with a standard chemotherapy regimen with or without the tucatinib. Serial brain scans were obtained in order to measure the response of the brain metastases to the treatment. These were typically MRI scans of the brain.

The study results showed that the use of tucatinib in patients with breast cancer involving the brain reduce the risk of the growth of their brain disease by about two-thirds and improve their overall survival by at least 6 months. These results have recently been published in a more complete form in the Journal of Clinical Oncology. And these results really strongly support the use of tucatinib in combination with the standard chemotherapy regimen of trastuzumab and capecitabine in patients with HER2-positive metastatic breast cancer involving the brain.

Although neither of the new approaches I've just described cure the majority of patients treated with either the primary CNS lymphoma or brain metastases from breast cancer, both describe new approaches that really potentially move us further along the road to having more effective treatments for patients with brain tumors. These studies are also outstanding examples of why well-done clinical trials that carefully test and evaluate the beneficial effects as well as the toxicities of new cancer treatments are critical to our goal of finding new therapies to treat our patients with cancer. Thanks very much.

ASCO: Thank you, Dr. Lesser.

Next, Dr. Michael Williams will discuss several studies that looked at new ways to treat different types of lymphoma. 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. He is also the Cancer.Net Associate Editor for Lymphoma.

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

Dr. Williams: Hello. This is Dr. Michael Williams. I'm a professor of medicine at the University of Virginia hospital in Charlottesville, Virginia, where I'm chief of the hematology oncology division and the physician lead for cancer services here at UVA. I have a few disclosures, clinical trial grant support from Janssen and Pharmacyclics to the University of Virginia. I've received honoraria for medical education conferences from Xian Janssen, and I have been a consultant for Kite Pharmaceuticals in the past. So what we're going to talk about today are some of the highlights in lymphoma that were presented at the recent virtual meeting of the American Society of Clinical Oncology focused on lymphoma. So the field continues to move forward very rapidly. It's really a dynamic time for advances in treatment of lymphoma and related disorders. The exciting thing is that patients in the not-too-distant past may have had limited options, especially in the setting of recurrent lymphoma. We now have new approaches that are really quite interesting, quite effective, and I think are going to change the way we practice for these particular diseases.

So the first of these I'm going to talk about is for classical Hodgkin lymphoma, also called Hodgkin's disease. So the good news is here, that the vast majority of people with Hodgkin lymphoma are cured by their frontline therapy but not all do achieve a remission, or if they do, they may relapse a year or 2 or sometimes later after their initial therapy. And these patients, historically, have not had as good of a long-term outcome as those who remained in their initial remission. So investigators from an international team of lymphoma experts conducted the KEYNOTE-204 study that compared an immune checkpoint inhibitor - it's a form of immunotherapy called pembrolizumab - versus a standard agent brentuximab vedotin, which is a drug antibody conjugate that delivers a chemotherapy agent directly to the Hodgkin tumor cells. So these were patients who had either not responded to their initial treatment, in other words were considered to be primary refractory, or had relapsed later. Many of them relapsed within 12 months, which is, again, a worrisome timing for relapse in that those patients may be more chemotherapy resistant to traditional treatments.

So in this study, it was a 1-to-1 comparison of about 300 patients. And the study found that those who received the checkpoint inhibitor pembrolizumab had a better response in terms of their remission rate and a more long-lasting response than those patients treated with brentuximab vedotin. At 12 months, about 54% of patients remained in remission as opposed to about a third of patients on brentuximab. Although, there were some continued relapses over the next year, there were some patients who achieved more durable response. So it was a very encouraging finding. The side effects were as would be expected. There were some autoimmune problems with the immunotherapy checkpoint inhibitor and peripheral neuropathy in those who got brentuximab. So these investigators concluded that for patients with this form of relapsed and chemotherapy-resistant Hodgkin's lymphoma, that pembrolizumab should be considered the preferred treatment option and a new standard of care for these patients.

Now, the second trial that we'll talk about relates to a specific form of non-Hodgkin lymphoma called lymphoplasmacytic lymphoma or Waldenstrom macroglobulinemia. This is a lymphoma where an abnormal immunoglobulin, a high molecular weight IgM, is produced. That can cause problems of hyper viscosity and headaches, vision changes, shortness of breath, in addition to some lymphoma-related symptoms. And what they did is compared 2 targeted agents for people who needed treatment, whether they were relapsed or had not had prior treatment at all for their Waldenstrom's. And the drugs that they chose were Bruton tyrosine kinase, or BTK, inhibitors. These are a very active class of drugs in B-cell lymphomas including Waldenstrom's. And the first of these that became available several years ago and was FDA approved is ibrutinib, and a second agent more recently approved is zanubrutinib. The latter being a bit more targeted to the molecule that we're trying to inhibit in the tumor cells. And it's similar in many ways to a third drug that's available called acalabrutinib.

But in this study, they're comparing ibrutinib with zanubrutinib. And what they found is that, in about 200 patients, that both drugs were very effective in achieving a response. Slightly higher response rates for zanubrutinib, but really no significant difference in the progression-free and overall survival for these patients. So both drugs were very active and very reasonable for treating patients. There were fewer side effects, however, with zanubrutinib, in particular toxicities such as the development of atrial fibrillation and diarrhea or bruising and bleeding, which happened in a small percentage of patients on ibrutinib. So those side effects seemed to be less with the more targeted drug zanubrutinib. So they appeared to be similar in efficacy but perhaps a better safety and toxicity profile with zanubrutinib. Now, ibrutinib is approved in the United States for relapsed Waldenstrom macroglobulinemia. Zanubrutinib is approved for mantle cell lymphoma, so not for Waldenstrom.

So the final entity that I want to discuss is really using a treatment that many of you no doubt have read about. There's been a lot in the news about the use of CAR T-cell, or chimeric antigen receptor T-cell therapy. So this is a form of cellular therapy. And by that, I mean that in patients who have relapsed aggressive lymphoma, usually diffuse large B-cell, a patient who has relapsed disease has T-cells. Those are part of their immune cellular defenses. And those T-cells are removed and they're genetically reprogrammed and then expanded and reinfused to patients. So they're reprogrammed so that the immune effects are targeted against the patient's lymphoma cells. So this is an approved therapy in aggressive relapsed large B-cell lymphoma. But at this meeting, investigators from a number of centers in the United States reported the interim results of a study using a CAR T-cell called axicabtagene ciloleucel, or Axi-cel, for patients with indolent or low grade lymphoma that, nonetheless, is recurring, needs treatment, and has been resistant to at least 2 or more prior therapies.

So I'm going to focus in this study on the results with follicular lymphoma. They did also study a small number of patients with another type of indolent low-grade lymphoma called marginal zone. But looking at the follicular lymphoma patients, they were heavily pre-treated. Most of the patients had had 3 or more prior therapies. Most of them were refractory or, in other words, resistant to the current and the most recent chemotherapy they had received. And about a quarter of the patients had had a prior stem cell transplantation for relapsed disease but had now relapsed even after that therapy. And what they found in the first 80 follicular lymphoma patients they studied is that 95% of them responded and 81% achieved a complete remission. The duration of response was really quite good. So with a follow-up of a little over a year, about two-thirds of patients were still in remission. Whether these patients may be cured of their follicular lymphoma or may experience a later relapse is going to require more follow up, but very promising early results for this treatment of patients with otherwise resistant follicular lymphoma.

There are significant side effects with this type of therapy, including something called cytokine release syndrome, which is like an intense inflammatory reaction. Fortunately, the severe forms of this occurred in a minority of patients, under 10%. There can also be neurologic events that can range from tremor or confusion, and rarely even patients becoming unresponsive. Fortunately, most everyone recovers from this. And in this trial, the more severe forms of these neurologic events occurred in about 15% of patients. So a very promising early set of data for another group of lymphoma patients, in addition to those with large cell lymphoma. So if you are in a situation of highly resistant and progressing follicular lymphoma, including follicular lymphoma that may have transformed from the lower grade into a higher grade large cell lymphoma, then considering a CAR T-cell therapy or a clinical trial of other novel approaches is certainly worth considering.

And I'll finish by just saying that it's a fast-moving field. There's a lot of benefit if you have a newly diagnosed or a relapsed lymphoma to talk with your oncologist and consider whether a second opinion may be in order and what clinical trials might be relevant for your situation because, nowadays, we often find that taking part in such a trial provides access to some of these very promising new agents and allows us to move the field forward and bring these newer treatments online so that they can benefit as many patients as possible. So a very exciting time in the field of lymphoma, lots of important new data presented at ASCO, and I'll look forward to updating you on future advances in another podcast.

ASCO: Thank you, Dr. Williams. Learn more about the research presented at the ASCO20 Virtual Scientific Program at www.cancer.net/blog, and subscribe to Cancer.Net podcasts on Apple Podcasts or Google Play to catch up on the other episodes in the Research Round Up series.

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, germ cell, and kidney cancer.

This podcast will be led by Dr. Sumanta (Monty) Pal, Dr. Neeraj Agarwal, Dr. Timothy Gilligan, and Dr. Tian Zhang.

Dr. Pal is co-director of City of Hope's Kidney Cancer Program and is the head of the kidney and bladder cancer disease team at the institution. He has served in a consulting or advisory role for Astellas Pharma, and Bristol-Myers Squibb.

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 Astellas Pharma, Bristol-Myers Squibb, Nektar Therapeutics, and Merck.

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

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 Bristol-Myers Squibb and Merck.

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

Dr. Pal: Hi. I'm Dr. Monty Pal from the City of Hope. I'm joined today by Dr. Neeraj Agarwal from the Huntsman Cancer Institute and University of Utah, Dr. Timothy Gilligan from the Cleveland Clinic Taussig Cancer Institute, and Dr. Tian Zhang from Duke Cancer Institute. Today we're going to discuss 3 ongoing clinical trials in prostate, germ cell, and kidney 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 a 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's 2020 Genitourinary Cancers Symposium. 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 visit the show notes for the episode on Cancer.Net.

Now, the first trial we're going to discuss is the KEYNOTE-641 trial for prostate cancer. [Study of Pembrolizumab (MK-3475) Plus Enzalutamide Versus Placebo Plus Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-641/KEYNOTE-641)] Dr. Agarwal, can you tell us who this study is designed for?

Dr. Agarwal: This trial is designed for patients with advanced prostate cancer, or metastatic prostate cancer, who are experiencing disease progression on standard androgen deprivation therapy, a state known as castrate resistant prostate cancer.

Dr. Pal: And if you see these patients in your clinic right now, what is the current standard of care?

Dr. Agarwal: The most commonly utilized [treatments for] these patients include drugs which block androgen signaling inside the prostate cancer cell. And one of the most commonly utilized drugs is enzalutamide followed by abiraterone.

Dr. Pal: Tell us a little bit about how this particular study aims to improve or change the current standard of care.

Dr. Agarwal: Early clinical data showed that adding the immunotherapy agent pembrolizumab to enzalutamide may improve survival outcomes. The response rates in that smaller study were meaningful and were very promising. Based on those earlier data, this trial has been designed and is asking two main questions. Number one, whether adding the immunotherapy agent pembrolizumab to enzalutamide will improve overall survival. And the second question is, whether adding pembrolizumab to enzalutamide will delay disease progression.

Dr. Pal: Are there any risks that patients should be aware of with this regimen?

Dr. Agarwal: Both agents are very commonly utilized for many years now in oncology clinics. Enzalutamide is an oral pill which blocks androgen signaling and is associated with side effects such as fatigue, muscle loss, bone loss, falls, and many others which are relatively easy to manage over time. Pembrolizumab is an intravenous therapy approved for multiple cancer types, and is associated with immune-related side effects. Many of these can be severe in 4 to 5 percent of patients receiving pembrolizumab. These can include diarrhea, abnormal liver function tests, or liver toxicity, a skin rash, lung toxicity, which can include pneumonitis [or lung inflammation]. But most of these side effects can be managed as long as they are promptly detected. So I think education and close monitoring with oncologists is the key for early prevention and management of the side effects.

Dr. Pal: Those are great tenets, not just for this clinical trial but in using these agents in general. Thanks a lot. And final question for you, Dr. Agarwal. Is this trial still open right now? And if so, when do you think we might see some results from it?

Dr. Agarwal: This trial is open across the United States and different parts of the world. And the primary results, early results, will be available, I'm hoping, in 2023, in the middle of 2023.

Dr. Pal: Well thank you for that excellent overview, Dr. Agarwal. I'm going to turn my attention now to Dr. Gilligan to discuss a topic that we don't often have on this podcast. But this is nonetheless a critical disease space for us to discuss. Dr. Gilligan is going to tell us about the P3BEP clinical trial in testicular cancer. [Accelerated v's Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours (P3BEP)] Dr. Gilligan, can you tell us a little bit about who this study is designed for?

Dr. Gilligan: Yes, germ cell tumors are cancers that start in the reproductive cells, most commonly in testicles of adolescent or adult men. But germ cell tumors can also start in children - typically not in the testicles but elsewhere in the body - and they can start in women in the ovaries or elsewhere. In children, we sometimes see [germ cell tumors starting in the brain]. Those are not included in this trial. But basically, everybody else with germ cell tumors are eligible for this - men, women, and children - if they have a poor or intermediate prognosis. And just to clarify one more piece about that, this is for people who have advanced stage disease. Again, men, women, or children with advanced stage metastatic germ cell tumors, as long as it didn't start in the brain. And as long as their prognosis is in the intermediate or poor risk category, not the good risk category.

Dr. Pal: So glad that you pointed that out, Tim. I have to tell you that I gave this incorrect label of a testicular cancer study, but critical for our listenership to know the germ cell tumors can occur both in males and females. Can you tell us a little bit about the current standard of care for the patients that are being [included] in this study?

Dr. Gilligan: Absolutely. Chemotherapy for germ cell tumors has been one of the huge success stories of modern oncology, and the cure rate is extremely high. Overall, [we cure about 96% of men with testis cancer.] However, when you start to look at advanced stage disease in intermediate and poor risk patients, the success rate goes down. It's about a 75% cure rate for patients with intermediate risk tumors and 60% for [those with] poor risk tumors. The standard of care has been the same for a long time. It's 4 cycles of chemotherapy called BEP, and that's what has produced those results. And while those results are good, we would like them to be a lot better.

Dr. Pal: So Dr. Gilligan, you've used this term intermediate and poor risk in the context of patients with germ cell tumor. Can you tell us a little bit about what intermediate and poor risk [means]?

Dr. Gilligan: Yes, it's based mostly on where the cancer has spread to and how high certain blood tests are. There are things called tumor markers which are proteins in the blood that are made by the cancer, and the higher those levels, the worse the prognosis. Similarly, if the cancer has spread to certain organs, such as the liver or the bones or the brain, organs other than the lungs, then patients have a poorer outcome and a poorer prognosis. The last category is men and women who have certain germ cell tumors that grow in the chest called extragonadal tumors. They also have a prognosis that's not as good as other germ cell tumors. So it's a little bit complicated, and for patients, when you see your oncologist, they can clearly tell you which prognostic category you fall into.

Dr. Pal: How does this study aim to improve or change the standard of care?

Dr. Gilligan: So mainly we'd like to get those numbers better. And I think the key idea in this study is that with chemotherapy, which is different than the kinds of drugs we talked about in the prior conversation, the philosophy is to basically give patients as much of a dose as they can safely tolerate. And the idea of this trial is that if we give the chemotherapy more frequently - if we kind of squeeze together the cycles so that rather than every 3 weeks we're repeating it every 2 weeks - can we get a better response in killing the cancer without having too much toxicity?

Dr. Pal: So they use this term in the title "accelerated." Is that what you're referring to there?

Dr. Gilligan: Yes. So if you think of chemotherapy as something that is repeated, we're repeating it sooner. And we used to give the patient 3 weeks to recover. On this trial, they're comparing that standard approach every 3 weeks to giving it every 2 weeks. In other words, we're making it denser. You get the chemotherapy faster. And the question is, will we cure more people that way or not?

Dr. Pal: And Dr. Gilligan, any known risks that patients should be aware of as they [consider] a study like this?

Dr. Gilligan: Well I think the risk with this approach is that we may increase toxicity without improving outcomes. Past attempts to do better than the standard treatment have not been successful. And the current standard treatment has been the standard for a long time as a result. We are hoping the new approach will be better, but we don't know until we try it, and it's possible that it will be more toxic.

Dr. Pal: When do you think we might see some results from this?

Dr. Gilligan: I don't know when we will see results. My guess is that it will be within a few years. Germ cell tumors grow quickly; they're aggressive cancers, so you tend to get your results pretty quickly, but I don't know exactly.

Dr. Pal: Dr. Gilligan, thank you for that excellent overview. Last, but certainly not least, we're going to turn our attention to Dr. Tian Zhang for discussion of a very important study in kidney cancer. [A Study of Bempegaldesleukin (NKTR-214: BEMPEG) in Combination With Nivolumab Compared With the Investigator's Choice of a Tyrosine Kinase Inhibitor (TKI) Therapy (Either Sunitinib or Cabozantinib Monotherapy) for Advanced Metastatic Renal Cell Carcinoma (RCC)] Tell us a little bit about this study and who it's designed for.

Dr. Zhang: PIVOT-09 is a study of a combination of a [novel] immunotherapy called bempegaldesleukin in combination with nivolumab compared to investigator-selected sunitinib or cabozantinib. So these are standard blood vessel blockers. The study is designed for patients with metastatic clear cell kidney cancer who have had no prior medication treatments and also measurable disease that can be followed on subsequent scans.

Dr. Pal: And when you're seeing these patients in clinic with metastatic kidney cancer, what is the current standard of care? What are you using to treat patients these days?

Dr. Zhang: We've known for a long time that kidney cancer will respond to these immune activating therapies, and [it has been demonstrated that a drug called IL-2, when given in high doses,] improved the overall survival for a subset of patients with metastatic kidney cancer and [produced] really durable complete responses for a small number of patients. However, it was highly, highly toxic, and there were lots of patients who ended up in the hospital. It had significant toxicities and patients were treated in the hospital for about a week at a time. So since about 2018, our standard of care immunotherapy options [have included] agents like ipilimumab and avelumab or the combination of pembrolizumab or avelumab with a blood vessel blocking agent. This is an easier way to give immune activating treatments in a more targeted fashion. [With this study we are testing] whether the IL-2 cytokine can be modified and given more in a more safe and effective manner.

Dr. Pal: This is an interesting drug. If I understand it correctly, we're taking IL-2 from yesteryear, a drug that we used more than a decade ago to treat patients with advanced kidney cancer, and we're retooling it a bit for patients to really enhance the efficacy, maybe really enhance the safety of the compound as well. Can you tell us how this compound's doing that?

Dr. Zhang: Right so bempegaldesleukin is a special formulation of IL-2. It's actually a pegylated form of the IL-2 cytokine, so it includes this polyethylene glycol molecule around the IL-2. And this pegylation allows that cytokine to be released slowly [in the bloodstream] so that in itself may improve the side effect profile. And then it also activates the tumor fighting subset of immune cells, T cells and natural killer cells in the tumor microenvironment, without activating other suppressive T cells. So the thought from preclinical studies is that bempegaldesleukin, because of its pegylated form, will actually decrease the side effects while activating the tumor fighting cells in the tumor microenvironment.

Dr. Pal: And in this trial, how will success be evaluated? How will we know the treatment is working, that it's positive?

Dr. Zhang: So the primary objective for this particular trial is a composite of objective responses as well as overall survival, and then secondary objectives include progression free survival - so lengthening time until disease progression - as well as evaluating the safety of the combination and the quality of life for patients who are treated on this combination.

Dr. Pal: Now I remember IL-2, the drug that you referred to, from more than a decade ago, giving it to patients and certainly it came with a lot of toxicity. What are some of the toxicities of patients receiving bempegaldesleukin should be aware of?

Dr. Zhang: Some of the early phase 1 trials that evaluated bempegaldesleukin found that some of the toxicities included low blood pressure as well as syncope where patients would feel lightheaded [or faint,] headaches, edema, swelling in their legs and fluid buildup, as well as infusion reactions. And I think we should also think about the immunotherapy-related toxicities of nivolumab where we're giving it in combination. So diarrhea, rashes, endocrine dysfunction are pretty common. So those would be some of the expected side effects of the immunotherapy cohort. And then we shouldn't forget about the control cohort treated with standard sunitinib or cabozantinib, and those side effects would include hypertension, hand foot syndrome or other rashes, diarrhea, nausea, hypothyroidism, and loss of protein in the urine.

Dr. Pal: Right. Well a final question for you Dr. Zhang. Is this trial still open to patients, and if it is, when do you think we might see some results from it?

Dr. Zhang: Yes, the trial is still open. It's enrolling up to 600 patients total and it's currently open globally in the U.S., Mexico, South America, Asia, Russia, and Australia. I'm hoping we will see results from this phase 3 trial in the next 2 to 3 years.

Dr. Pal: Well thank you very much, Dr. Zhang, Dr. Gilligan, Dr. Agarwal. 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. Thanks so much for listening.

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

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.

Every year, the ASCO Annual Meeting brings together attendees from around the globe to learn about the latest research in the treatment and care of people with cancer. This year, attendees from 138 countries worldwide gathered virtually for the ASCO20 Virtual Scientific Program, held Friday, May 29 through Sunday, May 31.

In the annual Research Round Up podcast series, Cancer.Net Associate Editors answer the question, "What was the most exciting or practice-changing research in your field presented at the ASCO20 Virtual Scientific Program?" In this episode, editors discuss new research in the fields of head and neck cancer and melanoma.

First, Dr. Ezra Cohen will discuss new research in squamous cell carcinoma of the head and neck and adenoid cystic carcinoma. Dr. Cohen is Co-Director of the San Diego Center for Precision Immunotherapy, Associate Director of Translational Science and leads the Solid Tumor Therapeutics research program at Moores Cancer Center at UC San Diego Health. He is also the Cancer.Net Associate Editor for Head and Neck Cancers.

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

Dr. Cohen: Hi. This is Dr. Ezra Cohen from University of California, San Diego, Moores Cancer Center. And today I'll be reviewing head/neck cancer abstracts from the American Society of Clinical Oncology Annual Meeting. I have consulted for Merck in the past.

As all of us know, this meeting was virtual this year, but we had an opportunity to see the broadcasts through the virtual website. And there were a few abstracts that I thought were relevant to not only current standards of care but also to the future of research in head/neck cancer. The first one I'll talk about is a Japanese study that compared post-operative chemo radiotherapy of 3 weekly cisplatin versus weekly cisplatin in high-risk patients with squamous cell carcinoma of the head and neck. This was indeed an adjuvant trial or a post-operative trial, and really addressed an important question in the field that had been controversial and perhaps continues to be going forward.

The investigators compared a dose of 40 milligrams per meter squared given every week versus the standard 100 milligram per meter squared of cisplatin given every three weeks and assess patients for local-regional control and overall survival. Interestingly enough and as opposed to some prior reports, the combination of weekly cisplatin and radiation actually proved to be superior with respect to both local-regional control and survival while providing a regimen that was fairly well-tolerated and in the aggregate actually had a lower toxicity rate than the every 3 week cisplatin, suggesting that at least at 40 mg per meter squared, we may have a regimen that is in the post-operative setting more efficacious, and better tolerated, and that it may be time to revisit standards of care or at least to perhaps accept 2 different standards of care in the post-operative setting; one being high dose every 3 weeks cisplatin and the other being weekly cisplatin.

The other relevant abstract from the oral session was another randomized trial, this time from South Korea. Looking at adenoid cystic carcinoma, here patients were randomized to either receive a vascular endothelial growth factor receptor inhibitor named axitinib vs. placebo in patients with metastatic disease. This class of agents that axitinib belongs to has been noted to be active in adenoid cystic carcinoma for some time, but there had never really been any randomized trials comparing axitinib to any treatment and certainly not to observation or placebo. Fifty-seven (57) patients were enrolled and progression-free survival was the primary endpoint, in fact, 6-month progression-free survival. And what the investigators found was that this was much better in the axitinib patients versus placebo. In fact, about 70% of patients in the axitinib arm failed to progress and were still alive versus only 23% in the placebo arm. Now, this was not a large enough trial to change registration or the label of the drug, but it certainly, for patients with adenoid cystic carcinoma who have very few treatment options, does provide a therapy that now is at the very least validated through a randomized phase II trial and gives us a little bit more confidence in using this entire class of agents in patients with adenoid cystic carcinoma.

One of the other targeted therapy studies that I think is also worth highlighting from the meeting was that using tipifarnib in patients with HRAS mutations. This was a study conducted across several different cancer types, but the most commonly enrolled patients and, in fact, a specific cohort were for patients with head/neck squamous cell carcinoma. And interestingly enough, the investigators having enrolled 18 patients found an overall response rate of 56%, arguably much better than we would be able to do with chemotherapy in these patients or any other targeted agent for that matter. And again, not a study that would change the label or standards of care but certainly worthwhile watching the efficacy of this agent tipifarnib going forward in patients with HRAS mutations.

And then from the poster discussion session, I think we saw some interesting data that may be a prelude to the future, especially with immunotherapy. Christine Chung presented the experience of cetuximab and nivolumab, an EGFR and a PD-1 antibody in combination, and found that to be quite active, again, in a non-randomized manner but certainly enough activity to think about taking that regimen forward. Dr. Roger Cohen presented the monalizumab and cetuximab data in patients with recurrent or metastatic disease in this time in a cohort that were both platinum and PD-1 refractory, so a heavily pre-treated patient population, and very nicely finding a response rate of 20% in patients with squamous cell carcinoma in the head/neck. And then lastly, along the lines of immunotherapy, an update on the data within ICOS agonist GSK3359609 in combination with pembrolizumab in patients who were treatment naïve with head and neck squamous cell carcinoma or at least PD-1 treatment naïve and again finding some promising activity with a response rate of about 24%.

The latter 2 trials, the monalizumab-cetuximab and the ICOS agonist pembrolizumab studies, are in fact now moving on to Phase III studies. And so again, there may be a change in the standard of care using some novel I-O regimens, and it's something to look out for in the future.

Thank you for listening to this review of head and neck cancer abstracts at the American Society of Clinical Oncology Annual Meeting and have a nice day.

ASCO: Thank you, Dr. Cohen.

Next, Dr. Ryan Sullivan will discuss several studies across the field of melanoma treatment. Dr. Sullivan is a medical oncologist and Attending Physician in the Division of Hematology/Oncology at Massachusetts General Hospital. He is also the Cancer.Net Associate Editor for Melanoma and Skin Cancer.

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

Dr. Sullivan: My name is Dr. Ryan Sullivan. I am the associate director of the melanoma program at Massachusetts General Hospital in Boston, and I'm here today to give a summary of some exciting data that was presented at the 2020 Annual ASCO Meeting which, of course, was presented virtually. I have a few disclosures, including that I have served on advisory boards for a number of companies whose data was presented, including Bristol Myers Squibb, Merck, Novartis, and Iovance. I'd like to start, really, by thinking about how a patient's journey with melanoma begins and then moves on through various stages of treatment, because there were a number of very interesting abstracts and presentations presented this year that include important breakthroughs in many different steps in the patient's journey. The first, of course, is a diagnosis, and soon after a diagnosis, often, the next step is surgery.

There's been more and more data about treatment before surgery as a way of potentially improving outcomes for patients who have a significant amount of tumor in place, typically in lymph nodes. Treatment before a planned surgery is called neoadjuvant therapy. There's also been breakthroughs, and, at this year's ASCO, updates on these breakthroughs in treatment after surgery, which is done with curative intent. We call that type of treatment adjuvant therapy. There were some updates to studies in patients who have newly diagnosed metastatic disease, and then there were some very interesting presentations about data of patients who were treated after the first type of treatment, for a patient with metastatic disease, was ineffective, demonstrating some really promising second and even third lines of treatment that may be available for patients.

So I'll start with that neoadjuvant therapy. This is, again, treatment that's given before somebody who could have surgery with curative intent, and the idea behind this is to potentially improve the outcomes of patients. It's also a really important type of research treatment because we can learn a ton about how tumors respond or don't respond to certain types of treatments, and there is a really wide path that's been created by the breast cancer community, who pioneered this type of treatment, and demonstrated that new and effective therapies can actually make it to the standard of care for patients in this setting. In melanoma, we've looked at a lot of the breakthrough therapies that have been approved in the metastatic and the stage 3 after surgery setting, including immunotherapies and BRAF-targeted therapies.

And the background is a number of trials have occurred, and 1 very prominent group that has been leading a lot of these efforts is the group in the Netherlands, and Dr. Christian Blank presented some data on a follow-up study of almost 100 patients, who received a combination of two drugs, ipilimumab and nivolumab, at a schedule in dosing level that had been determined to be, probably, as effective as higher doses and more toxic therapy, but had a better safety profile than other regimens. That trial was called the OpACIN-neo, which randomized patients to 3 different dosing levels and strategies. So patients receive this, and then, in a really cool fashion, they knew that almost 70 or 80% of patients would have a major response to therapy - that was based on other data - but they also wanted to see if they get away with less surgery. And so what they did was, patients who had major responses were offered a smaller surgical resection. Patients who didn't have major responses ended up having a complete surgical resection of lymph nodes, and then they just followed along.

And really, it was less a trial that will prove that this is the right thing to do, but more a trial to be built upon. And as more and more data comes out, this could be a strategy that we utilize for patients, where they may only get 2 doses of a treatment, and then if they have a major response to therapy, they could just be followed closely thereafter. So this trial is called the PRADO trial. Christian Blank was the presenter, and I would say it's promising, and maybe practice-changing as more data comes out and larger trials are performed to compare this strategy with other more standard strategies.

The next set of data that was presented that's really interesting is in the adjuvant setting, so again, these are patients who've had surgery to cure them of their melanoma, but they're at high risk of the melanoma coming back and so receive treatment after surgery - we call that adjuvant therapy - to reduce the chance of disease coming back. There were 2 trials that were updated at this year's ASCO. One was the KEYNOTE-054 trial. This is randomizing a drug called pembrolizumab, an anti-PD-1 blocking drug, versus placebo. This trial was a positive study, and was published a few years back, and pembrolizumab was FDA approved, a few years back, for patients who have high-risk stage 3 melanoma, who have completed surgery. The follow-up data continues to show the superiority of the pembrolizumab compared to patients who received placebo, and importantly, that superiority is across virtually every subgroup that was analyzed, and demonstrates that this approach continues to be a standard approach for patients with melanoma who are high risk and have stage 3 disease that's been resected.

A similar group of patients were enrolled on to a trial called the COMBI-D study. This is a trial that randomized BRAF mutated patients with stage 3 melanoma, whose disease had been removed, and received either dabrafenib and trametinib, which is a BRAF and MEK inhibitor, or 2 placebos. Again, this trial previously read out as a "positive study," and this regimen has been FDA approved for this patient population. Importantly, the data continues to look really good.

BRAF targeted therapy, initially, it was thought that it might prevent relapse during the treatment time and a little after the treatment time, but there was thoughts that the effects of it, and the effectiveness of it, might actually wane over time, but that doesn't seem to be the case. This is a 5-year update, and it still appears that this combination is associated with cures in patients with stage 3 melanoma, who would not have been cured if they didn't receive it. So again, really important follow-up data, and strengthens the idea that this is a very reasonable alternative to anti-PD-1 antibody therapy like pembrolizumab, which was described just a few minutes before, in the same setting, but in this case in patients who had BRAF mutated melanoma.

There were some important trials, and one was a retrospective study of therapy in patients who had metastatic melanoma or unresectable disease, so this is melanoma that either presented in a widespread fashion, or was previously diagnosed and treated with surgery, maybe adjuvant therapy, and then metastasized. The standard front-line therapy is really 1 of 4 options: anti-PD-1 antibody with either nivolumab or pembrolizumab; BRAF targeted therapy, if a patient has a BRAF mutation; combination nivolumab and ipilimumab; and then enrollment onto a clinical trial.

Many sets of data are out there in publications about the combination of ipilimumab and nivolumab in the frontline metastatic setting, and while it is associated with the highest response rates of immunotherapy in patients with melanoma, it's also associated with very high toxicity rates. And so ultimately, a decision is typically made upfront, and we balance the risk of the toxicities with the benefit of the therapy, and a decision is made about what to give. If a patient receives ipilimumab and nivolumab in the frontline setting, and then their tumor progresses thereafter, there aren't great second-line options unless a patient has a BRAF mutation, and then BRAF targeted therapy with 1 of the 3 BRAF/MEK combinations is an option.

Patients who receive single-agent PD-1 therapy second-line treatment after disease progression-- could be single-agent ipilimumab, which was the first of these new immunotherapies to be approved. And so one of the questions, though, has been could you give combination ipilimumab plus a PD-1 blocking drug in that second-line setting, and have better outcomes than if you just gave ipilimumab? There's no randomized trial looking at this, but a group in Australia did a retrospective analysis and identified patients who received either single-agent ipilimumab, or a combination ipilimumab plus a PD-1 blocking drug. I should say that I was part of this retrospective analysis, and some of our patient data was part of this analysis. What was shown was that there were improvements in the response rate for patients who received combination ipilimumab plus a PD-1 blocking drug, versus single-agent ipilimumab, and it appeared that the benefit was about twice as good, meaning the response rate was about twice as good, and patients had about twice as solid progression-free survival, and they lived twice as long.

Now, any retrospective analysis is really hard to make practice-changing decisions on, we really like randomized trials that are prospective, and so that data doesn't exist. There is a randomized prospective trial currently enrolling patients in the U.S. Cooperative Group setting, and it's randomizing patients, after PD-1 blocking drugs, to either ipilimumab or a combination of ipilimumab and nivolumab. So until that trial reads out, we won't know for sure that this is the right strategy, but the data certainly was suggestive that combination ipilimumab plus the PD-1 blocking drug makes sense. There actually also was data presented in a prospective study, 1 arm, so it wasn't randomized, that patients who'd been on a PD-1 blocking drug and then switched to pembrolizumab, a PD-1 blocking drug, and a low dose of ipilimumab after their disease had progressed on the PD-1 blocking drug. In that study, response rates were in the mid-20% range - I believe it was 27% - which is higher than we've seen with ipilimumab in that setting, for which the response rate would be expected to be about 10-15%. And so again, further data this time, prospective data, suggesting that there is an improved outcome for combination therapy in the second line.

Importantly, toxicity, which we worry a ton about in the frontline, seemed to be less of an issue in the second line because we'd be comparing against ipilimumab, which is more toxic as a single agent than anti-PD-1 blocking drugs is, and in the second line, it seemed like combination therapy didn't seem to be any more toxic than single-agent ipilimumab. I think we also need to see the randomized data to firmly change the standard of care forever, but I think since this is a regimen that can be offered as standard care, with commercial product, it's an option for patients, and there's now data that really supports its use.

The last study I'm going to talk about is a trial of a cellular product called lifileucel. In the '80s and '90s, in the National Cancer Institute, work led by Dr. Rosenberg and his colleagues, in the surgical branch there, developed the technique where they would remove a tumor, take out the T cells from the tumor, grow the T cells, expand them, and then give them back to patients after lymphodepleting chemotherapy, which would allow patients to receive and not destroy those T cells that were coming in, and then give IL-2 to grow those T cells and support them as they expand in the body. This is a very hard therapy to receive. At the NCI, it required patients to have an initial visit, have enough tumor to have it removed, be able to come back a few weeks later, have the tumor removed, and then the T cells had to grow, and we never really knew how many patients ended up showing up at the NCI to be evaluated for this, and then, ultimately, were treated. And so it is hard to know what to make of the response rates, which were remarkably high. As high as 50-55% in some studies when looking at the data. But the worry was that maybe only a quarter of patients that showed up ended up getting treated, and so the response rate would be a lot less, of all people that were screened.

And so there's real interest in finding a commercial product that could not necessarily require the production of the cell product to be done at an individual institution, and certainly not 1 institution like the NCI, but that could be done centrally and commercially. And so lifileucel is a product that comes from patients' tumors, again, requires a patient to have surgery, the tumor gets removed; it gets sent to a central laboratory where the T cells are isolated, grown, expanded; and then when the product is ready, patients, if they're still well, are able to be admitted to the hospital get lymphodepleting chemotherapy, receive the cells, receive IL-2, and then see what happens. The data that was presented at ASCO was an update from a year ago, which showed that patients-- and all of these patients had had anti-PD-1 antibody therapy, probably 70 or 75% of patients had ipilimumab, so heavily pretreated population of patients, and the response rate of patients who were able to receive treatment was 37%. So that's not everybody, obviously, and that's not even half the patients, but that's a pretty impressive response rate, for patients who weren't previously responding to immunotherapy.

There's a lot of excitement about this data, and more importantly, there was data that suggested that 82% of patients that showed up for surgery ended up getting treated. So we actually have a denominator of patients screened. Ninety-four (94%), 95% of patients were able-- a product was able to be made, so the concerns about whether or not this is for most patients that end up having surgery, the answer is they probably can make a product for just about everybody. This is probably the 1 presentation, in the oral abstract session at ASCO, in the melanoma program, that is a regimen that would be new, and potentially practice-changing in the near future. So that's exciting, and we're hopeful that that will be an option for patients in the near future.

With that, I'd like to finish by saying it was another great year for the melanoma research community. Lots of really interesting data presented. I touched upon some of the highlights, but lots of other really cool trials and data presented, as well, and I remain very hopeful for the future of, not just our research community, but more importantly for our patients, who are going to benefit from this wonderful research that's being done, which will hopefully continue to lead to better outcomes for our patients. And with that, I thank you for your attention.

ASCO: Thank you, Dr. Sullivan. Learn more about the research presented at the ASCO20 Virtual Scientific Program at www.cancer.net/blog, and subscribe to Cancer.Net podcasts on Apple Podcasts or Google Play for additional episodes in the Research Round Up series, released throughout the summer.

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.

Brielle Gregory: Hi, everyone. I'm Brielle Gregory, 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 hepatitis B virus. Our guests are Dr. Andrew Artz and Dr. Jessica Hwang. Dr. Artz is an associate clinical professor in the Department of Hematology and Hematopoietic Cell Transplantation, the director of the Program for Aging and Blood Cancers, and the deputy director of the Center for Cancer and Aging at City of Hope Comprehensive Cancer Center in Duarte, California. Dr. Hwang is a tenured professor in the Department of General Internal Medicine in the Division of Internal Medicine at the University of Texas MD Anderson Cancer Center in Houston, Texas. Thanks for joining us today, Dr. Artz and Dr. Hwang.

Dr. Hwang: Thank you, Brielle. Nice to be here.

Dr. Artz: Yes. Likewise, Brielle. Thank you so much.

Brielle Gregory: Today ASCO is publishing a new provisional clinical opinion on hepatitis B virus screening and management for patients with cancer prior to therapy. Dr. Artz and Dr. Hwang served as the co-chairs for this provisional clinical opinion. Before we begin, we should mention that Dr. Artz has no relationships to disclose related to this provisional clinical opinion and Dr. Hwang has one relationship to disclose. Their full disclosure statements can be found on Cancer.Net.

Now, let's talk a little bit about what this provisional clinical opinion means for people with cancer and those who care for them. Dr. Artz, to begin, what is a provisional clinical opinion and how does it influence cancer care?

Dr. Artz; Yes. Absolutely. We appreciate that new information develops very quickly in oncology, and provisional clinical opinions are really a way to respond to the rapid information accumulation in the field. They're evidence-based guidances, and they're meant to offer timely direction to the ASCO membership, which means the physicians and the other providers in the oncology team. Usually it follows practice-changing information, and then there may be updates. Such is the case for this PCO, which was initiated in 2010, updated in 2015, and now we have the next version, the 2020 update that we're discussing today.

Brielle Gregory: So basically, these opinions are updates with the latest information to make sure that patients are getting the most up-to-date care as possible. Is that correct?

Dr. Artz: Yes. Absolutely.

Brielle Gregory: And Dr. Hwang, can you define for us what hepatitis B virus is and how it's connected to cancer?

Dr. Hwang: Hepatitis B virus infects the liver. In an acute setting, it can cause jaundice or yellowing of the eyes, yellowing of the skin, nausea, vomiting, abdominal pain. So that's really the acute phase. But oftentimes hepatitis can infect a person and not even cause any symptoms. This is a troublesome virus that can infect the liver, and once it infects the liver, it can live latently or very quietly in the liver for a long time, and maybe sometimes not even cause problems in certain people. But it can cause some really serious problems, like cirrhosis, which is hardening of the liver. It can even lead to liver cancer and a lot of complications from that because it's very difficult to control at that point.

But what I want to bring to mind today in our discussion is that hepatitis B can linger in a person's liver once infected. And should that person require some sorts of medication that would weaken the immune system - say, for instance, cancer treatments or chemotherapy or one of the newer agents - it's possible that a person's weakened immune system would allow the virus to just start growing and replicating and not be checked. And that can lead to liver complications during, as well as after, that cancer treatment.

Brielle Gregory: Thank you so much for explaining that. So going a little bit into this update, who should be screened for hepatitis B virus and when should people be screened?

Dr. Hwang: Well, that's a really important point, and one that we want to highlight today. Dr. Artz and I were able to participate in a group of really experienced clinicians to try to figure out who should be screened and how best to screen them. And the group really thinks that everybody should be screened who is about to get cancer therapy. So really all patients with any type of cancer, whether it's a cancer that affects a solid organ of the body or perhaps one of the blood cancer conditions. Any patient with any type of cancer really is at risk of having a potential complication if they have hepatitis B, so we just advocate that everybody get screened. It's just a simple blood test, and there are 3 hepatitis B blood tests, and they are routine tests available at all labs, and they're fairly easy to get and the results are available rapidly. So I think it's really just a good practice to get everybody tested before they start their cancer therapy so that they can be well protected.

Brielle Gregory: And I know you mentioned that there are 3 tests for hepatitis B. So can you describe what those 3 tests are?

Dr. Hwang: Sure. One test is called the hepatitis B surface antigen. And if this test is positive, this really is indicative of a patient having one of the more severe forms of hepatitis B, what we talk about in the medical world as being chronic hepatitis B. Another test is called a hepatitis B core antibody, and this is a test that's positive in anybody who's had a past infection with hepatitis B. So it can be positive in patients with chronic disease, but assuredly it is positive in patients with past infection. And then the third test is a test called hepatitis B surface antibody, and that's a protective antibody. It's good to have that one positive. So if a person has had a previous vaccination, this hepatitis B surface antibody will hopefully be positive and indicate that they are protected against the hepatitis B.

Brielle Gregory: And what are some of the problems that hepatitis B can cause during cancer treatment?

Dr. Hwang: Well, Brielle, I mentioned just a few minutes ago that once infected, the hepatitis B virus can linger in the liver of an infected person. And though it might not cause problems, I think that the cancer treatments, if they're immunosuppressive and they weaken a person's immune system, that could lead to the virus replicating and growing out of control, so that it could then lead to liver damage, what we call flares of the liver. It could also lead to really acute liver injury, even liver failure. And there are reports of death from liver-related complications in patients with cancer and underlying hepatitis B from their cancer therapy. So it's a really serious, potentially serious condition, this hepatitis B reactivation that we're talking about, and I think that's why it's really important for patients to be tested for hepatitis B before they receive their cancer treatment.

Brielle Gregory: Thank you so much for explaining that. And Dr. Artz, for people who have previously had hepatitis B, as Dr. Hwang just mentioned, there is a risk that some cancer treatments could lead to a hepatitis B reactivation. So what does ASCO recommend to help reduce that risk of reactivation?

Dr. Artz: Yes. I think it's a really important point for this virus that through appropriate monitoring and treatment, we can largely avoid the complications that were just discussed. And that's really the key point why testing is so important, that it's not only to identify problems that might emerge, but that we have an approach that is likely, for many patients, to avoid complications. Specifically, there are pill or oral medications that are well tolerated, don't interact with most chemotherapy, that would be offered to most patients with what we call chronic hepatitis B—that is, hepatitis B surface antigen—receiving anti-cancer therapies that are systemic—that is, pills or IV chemotherapy—would receive a treatment to prevent chronic hepatitis B from worsening. With some exceptions, in patients receiving hormone therapy alone for prostate cancer or breast cancer—those are some special circumstances where that has to be discussed with an HBV specialist.

Now, for another group of patients, those who had past hepatitis B where the danger of hepatitis B re-emerging is less, we recommend the treatment against hepatitis B in those cases where the treatments the patients will receive weaken the immune system to such a degree that the hepatitis B might re-emerge even in that situation. And those are what we call anti-CD20 antibodies, such as rituximab or stem cell transplant, are the ones that we're most concerned about. But in addition to the medications against hepatitis B, monitoring is a major part of this. So patients who are on medications—or even if they're not on medications, we've outlined a monitoring strategy for clinicians to follow that informs people about the tests, the blood tests they should get, and also to monitor patients past the time of completing chemotherapy because the virus can reactivate even after stopping therapy. And that's really important to know for people.

I think another key point is that in this PCO, we really talk about a collaborative approach, and HBV—now that we'll be identifying it more often, a lot of times patients and clinicians were unaware of its presence. We need to work with HBV specialists—that is, those who have a lot of expertise in HBV in certain situations as a team. And I think that collaborative approach, for situations that are more challenging and we need a more nuanced approach, will allow patients to receive individualized care that's based on their situation.

Brielle Gregory: So just to clarify, both for patients who currently have hepatitis B and patients who have in the past had hepatitis B, there are options for them to hopefully avoid some of the problems that were discussed earlier. Is that correct?

Dr. Artz: Yes. Absolutely. I think identifying hepatitis B is an opportunity to avoid future problems and really safely receive their chemotherapy with fewer complications, or less chance of complications from hepatitis B.

Brielle Gregory: Great. Well, thank you so much for your time and for sharing your expertise today, Dr. Artz and Dr. Hwang. It was so great having you.

Dr. Hwang: It's been a pleasure. Thanks, Brielle.

Dr. Artz: Yeah. It's been a real pleasure. Thank you again.

ASCO: 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.

Every year, the ASCO Annual Meeting brings together attendees from around the globe to learn about the latest research in the treatment and care of people with cancer. This year, attendees from 138 countries worldwide gathered virtually for the ASCO20 Virtual Scientific Program, held Friday, May 29 through Sunday, May 31.

In the annual Research Round Up podcast series, Cancer.Net Associate Editors answer the question, "What was the most exciting or practice-changing research in your field presented at the ASCO20 Virtual Scientific Program?" In this episode, 3 editors discuss new research in the fields of breast cancer, sarcoma, and palliative and supportive care.

First, Dr. Norah Lynn Henry will discuss 3 studies that exploring treatment options for different types of breast cancer. Dr. Henry is an Associate Professor in the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and is the Breast Oncology Disease Lead at the Rogel Cancer Center. She is also the Cancer.Net Associate Editor for Breast Cancer.

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

Dr. Henry: I'm Dr. Lynn Henry, one of the breast cancer experts from the Rogel Cancer Center at the University of Michigan. I would like to share with you a few of the research highlights related to breast cancer from the ASCO 2020 Virtual Scientific Program. I do not have any relationships to disclose related to any of these studies. There were many exciting trials presented at this conference for all types of breast cancer. Today I will highlight 3 key studies that will likely change how we treat patients with breast cancer. Before I start talking about the trials themselves, I'm going to give a very brief overview of the types of breast cancer. Then I will talk about an important study that looked at the use of surgery and radiation in patients whose cancer is metastatic or has already spread to other sites of the body at the time they are diagnosed with breast cancer. Then I will highlight some research that was presented on triple negative and HER2-positive metastatic breast cancer.

As a brief review, there are multiple kinds of breast cancer. Some breast cancers are called hormone receptor positive or estrogen receptor positive and are stimulated to grow by estrogen. We treat those cancers with anti-estrogen treatments to block estrogen or to lower estrogen levels. Other breast cancers are called HER2-positive. These are often more aggressive cancers, but because they have extra copies of the HER2 receptor, they often respond to treatments that block HER2. Finally, there are breast cancers that don't have any hormone receptors or HER2 receptors. These are called triple-negative breast cancer and are also often very aggressive cancers.

The first clinical trial I'm going to discuss was a relatively large trial conducted by the ECOG-ACRIN cooperative group. Of patients newly diagnosed with breast cancer, about 6% are actually found to have cancer in other sites in their body such as in the bone, liver, or lung, as well as in the breast. This is called de novo metastatic breast cancer. The goal of this trial was to determine whether patients in this situation should have surgery and radiation to treat the cancer in their breast in addition to drug treatment, or whether they should just have drug treatment for their cancer. In this trial, patients with de novo metastatic breast cancer of any type were treated with appropriate drug therapy for 4 to 8 months. The approximately 250 patients whose cancers improved with treatment were randomized to either have breast surgery and, if appropriate, radiation therapy, and then resume drug therapy or to just continue drug therapy the entire time. Overall, there was no difference in how long patients survived whether they had removal of the breast mass or not. In addition, the quality of life in the 2 groups of patients also appeared to be similar. These results confirm studies that have been conducted in other countries around the world and importantly examined whether surgery is appropriate in patients who are treated with modern therapies. It appears that surgery is not needed in most patients. This is important information for patients with de novo metastatic breast cancer who are trying to decide whether or not to have breast surgery as part of their treatment.

The next trial is called KEYNOTE-355 and examined the use of an immunotherapy drug pembrolizumab, also called Keytruda, in patients with triple-negative metastatic breast cancer. Immunotherapy is a treatment type that allows a patient's own immune system to help treat her cancer. We already have the FDA approved option of using a similar immunotherapy medication called atezolizumab, also called Tecentriq, in combination with a specific chemotherapy drug for patients whose cancer express PDL1. In this new KEYNOTE trial, pembrolizumab was combined with 1 of 3 possible chemotherapy options in patients with previously untreated metastatic triple-negative breast cancer. In this trial, in patients whose tumors had an increased amount of PDL1 on the cells and in the surrounding tissue, the addition of pembrolizumab to chemotherapy made it less likely for the cancer to progress compared to chemotherapy alone. Although this treatment combination is not yet FDA approved, all the drugs that were tested are already approved for use in other situations. These results are exciting because they will likely lead to new treatment options for patients with this type of breast cancer which can be quite challenging to treat.

Finally, I will highlight new results from the clinical trial called HER2CLIMB. This is a large phase 3 trial examining a new drug called tucatinib that is a pill that is designed to turn off the HER2 receptor. Patients who enrolled on this trial had previously been treated with multiple different treatments for HER2-positive metastatic breast cancer. All enrolled patients were treated with the anti-HER2 antibody drug trastuzumab, also called Herceptin, as well as a chemotherapy drug called capecitabine or Xeloda. In addition, two-thirds received the new drug tucatinib and one-third receive placebo. We learned about 6 months ago that this drug combination was pretty well tolerated by patients. And what is exciting about this trial is the patients who were treated with tucatinib had a longer time until their cancer progressed and lived longer compared to those who took placebo. As a result of this trial, the drug was approved by the U.S. Food and Drug Administration in spring 2020.

Because of the type of drug that it is, tucatinib is thought to treat cancer both outside and inside of the brain. This is important because many patients with HER2-positive breast cancer have the cancer spread to their brain. In fact, almost half of the patients enrolled in the trial had a history of metastases in the brain and many had active growing cancer in their brain at the time of trial enrollment. Importantly those patients with cancer in their brain obtained a similar benefit from the drug compared to those who didn't. Over half of patients with active cancer in their brain had at least a partial shrinkage of the cancer in their brain as seen on brain MRI when treated with tucatinib in addition to the other drugs, which demonstrates that tucatinib can get into the brain to treat the cancer. On average, patients with active cancer in their brain were more likely to live an average of 8 months longer as a result of taking tucatinib. This represents an exciting new treatment option for patients with HER2-positive breast cancer whose cancer has spread to their brain, and importantly this treatment is already available for patients.

Overall, there's a lot of exciting research going on across all the different subsets of breast cancer. As you can see, the results of these and many other important clinical trials were reported at the recent ASCO Annual Meeting and there are many more clinical trials ongoing that will hopefully result in the approval of multiple new effective treatments for breast cancer. In addition, there's research going on that is examining the impact of treatment on patients with breast cancer and trying to improve the lives of those living with breast cancer. Clinical trials are critical to the development of these new treatments.

Well, that's it for this quick summary of this important research from the ASCO 2020 Virtual Scientific Meeting. 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 cancer conferences. Thank you very much.

ASCO:Thank you, Dr. Henry.

Next, Dr. Vicki Keedy will discuss an international study that compared different treatment options for Ewing sarcoma, as well as new research in using immunotherapy to treat sarcomas. Dr. Keedy is an Assistant Professor of Medicine in the Division of Hematology/Oncology and the Clinical Director of the Sarcoma Program at the Vanderbilt-Ingram Cancer Center at Vanderbilt University Medical Center. She is also the Cancer.Net Associate Editor for Sarcoma.

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

Dr. Keedy: Hello, my name is Vicki Keedy, and I am the clinical director for Sarcoma at the Vanderbilt-Ingram Cancer Center at Vanderbilt University Medical Center. I am pleased to discuss with you some of the exciting research findings in the management of patients with sarcomas presented at this year's ASCO Annual Meeting. I have no direct conflict of interest, but my institution does participate in some of the trials using some of the immunotherapy agents discussed below. Sarcomas are a class of cancers made of many different types of connective tissue tumors. Thus, there is significant variety in the types of abstracts presented, making narrowing them down a difficult task. First, I will discuss a study that establishes the standard first-line treatment for patients with Ewing sarcoma. And then, I will finish by summarizing a few abstracts on the use of immunotherapy in various sarcomas.

Ewing sarcoma is a type of sarcoma that can start in either the bones or soft tissue, tends to occur in children and younger adults, but can present at any age. It is characterized by small, round blue cells and is considered sensitive to chemotherapy. Regimens using multiple chemotherapy agents are considered the standard first-line treatment. However, there's variation in the exact regimen with considerable differences between the treatments most commonly used in the United States versus that used in many European sarcoma centers. EURO EWING 2012, presented by Dr. Bernadette Brennan compared these 2 most common regimens to determine whether 1 is better in regards to improving survival but also to evaluate differences in toxicity. In this trial, 640 patients in 10 different European countries with newly-diagnosed localized or metastatic Ewing sarcoma were randomized to receive either the regimen called VIDE, most commonly used in Europe, or the regimen called interval-compressed VDC/IE, most commonly used in the United States.

VIDE consists of four drugs - vincristine, ifosfamide, doxorubicin, and etoposide - given together every 3 weeks prior to surgery. This is then followed by additional chemotherapy of a similar regimen post-surgery. VDC/IE consists of 2 different regimens alternating an every 2-week cycle. These are vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide, and these are received both before and after surgery. The results of this study showed an improved survival for patients who received VDC/IE that was both clinically and statistically significant. Its benefits seem to hold true for patients with both localized and metastatic disease regardless of age. Additionally, VDC/IE appeared to be less toxic with fewer episodes of neutropenic fever and fewer severe treatment-related toxic events, while also allowing patients to complete their treatment approximately 3 months earlier than patients receiving the VIDE regimen. This study demonstrates the importance of cytotoxic chemotherapy for patients with Ewing sarcoma and establishes interval-compressed VDC/IE as the standard of care.

Moving on to the next topic of immunotherapy and sarcoma, many of the abstracts presented this year related to use of those concepts in patients with various types of sarcoma. Due to the biology of sarcoma, the immune system is generally not able to recognize and attack sarcoma cells. Thus, this approach by itself has not shown much benefit in most sarcomas. However, as I mentioned, there are many types of sarcomas, and they do not all behave the same. We have seen signals of benefits in certain subtypes. Many of the abstracts presented this year evaluated immunotherapy in some of these specific subtypes or attempted to use it in combination with other treatments such as chemotherapy or radiation. Unfortunately, these studies were relatively small or did not compare the immunotherapy to a standard treatment, making it very difficult to make definitive statements about the results. But they do give us more insights into which types of sarcomas might benefit from this approach. These abstracts confirmed responses in undifferentiated pleomorphic sarcoma, synovial sarcoma, alveolar soft part sarcoma, in angiosarcoma, and Kaposi's sarcoma. There's still much work to be done to determine whether an immunotherapy approach is better than already approved treatments for these types of sarcomas, and it is essential to validate these results by treating patients with immunotherapy agents in the context of the clinical trial. I thank you for your time and hope you found this discussion helpful. I look forward to discussing more exciting results next year.

ASCO:Thank you, Dr. Keedy.

Next, Dr. Kavitha Ramchandran will discuss several aspects of research in supportive and palliative care that was presented at ASCO20. This type of care focuses on managing the symptoms and side effects of cancer and its treatment. It also includes support to help reduce the financial, emotional, and social effects of cancer.

Dr. Ramchandran is the Clinical Associate Professor of Medicine in the Division of Oncology at Stanford University, and the Medical Director of Palliative Medicine at the Stanford Cancer Institute. She is also the Cancer.Net Associate Editor for Palliative Care.

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

Dr. Ramchandran: Hi. It's wonderful to be here with you all today. My name is Kavitha Ramchandran, and I'm a clinical associate professor at Stanford University in oncology and palliative medicine and also have the pleasure of being the Associate Editor for Palliative Care on ASCO's patient education website, Cancer.Net. And I do not have any conflicts of interest to disclose related to the research that we'll be discussing today.

ASCO 2020 was a wonderful year in terms of palliative care education and research, and I am excited to share some of the highlights from that meeting with you all. We'll be talking about a few key research studies, and we'll be discussing a couple of different things. One, what are some of the novel approaches to symptom management in palliative care? Two, how do we actually assess risk in terms of our patients and how can we better stratify patients in terms of what type of treatments are best for them, and are there novel tools we can use? Three, how can we improve care by integrating palliative care early and often, both through a primary palliative care approach as well as a specialist palliative care approach? With that, let's go ahead and get started.

So in terms of symptoms, we had a really great discussion by Dr. Roeland from Mass General on several abstracts. The couple of abstracts that we're going to focus on here, one looked at armodafinil, which is a stimulant that has been often used for cancer fatigue. And the second was looking at cannabis compounds that have been thought about in thinking about nausea and folks who are suffering from nausea due to chemotherapy.

So our investigators that looked at armodafinil looked at armodafinil in patients who had glioma, and they wanted to see that if they used armodafinil in these patients, whether or not they would have an improvement in their fatigue. Now in the past, we know that there have been a number of studies that have looked at different types of treatments for fatigue, everything from steroids, to stimulants, to herbs, and what we found is that, consistently, stimulants have not been shown to improve fatigue. The things that have been shown to improve fatigue in small studies include steroids as well as American ginseng. Unfortunately, this was yet another negative study, and what we see here is that armodafinil did not improve fatigue and in fact, at the dose of 250 milligrams, might have increased insomnia or trouble sleeping. And so with that, I think we would make the assumption that we probably need to rethink our approach with stimulants in cancer-related fatigue and, for the majority of our patients, would make the decision that stimulants may not be the best course to improve fatigue.

On a positive note, we did look at patients who were receiving chemotherapy, and, in an Australian study, what they looked at was whether the addition of a THC plus CBD compound - now, this was both THC and CBD 1-to-1 - could improve nausea. And what they found is that, for these patients who all received the normal prophylaxis-- so they got Zofran. They got a D2 receptor antagonist, such as Compazine. If you added the THC-CBD compound, those patients actually had better nausea control, which was fantastic. However, they did also have some side effects from the THC-CBD, including dizziness, sedation, and disorientation. Yet despite these side effects, the patients really felt better, and so they were likely to continue using the cannabis. And they would actually choose to continue using the cannabis.

Moving on to a different note, there were a variety of different studies that looked at risk assessment, and can we actually identify which patients would benefit most from which intervention? And there was a couple of different types of studies here. One looked at the utilization of patient-reported outcomes to see whether or not we can identify patients who may be at more at risk for poor outcomes. We know Ethan Basch published, a couple years ago, a landmark study that showed that if you integrated patient reported outcomes, also known as PROs, routinely into cancer care, you could improve survival. So basically, if you looked at symptoms, evaluated those symptoms, and treated those symptoms early and often, people lived longer and lived better.

Now, can we use this data that patients give us through questionnaires on a regular basis, can we use this data in other ways? And we actually had a few studies here that looked at patients who had metastatic disease. And Dr. Batra et al. from Calgary looked at 1,300-plus patients, and what they found was that patients who had fewer symptoms tended to do better. And it seems like a kind of obvious point. If you have more symptoms, you might do worse, but I think the routine assessment of symptoms in patients and utilizing those symptoms is not done. So if we know that patients who have fewer symptoms might do better, may be able to use that data to see whether or not those patients might need more support or to use that data to see if those patients may not be the best patients for a clinical trial. Maybe we need to do symptom control first. So it does help us to risk-stratify and understand that patients that have more symptoms tend to have a shorter survival. Patients that have fewer symptoms tend to have a better survival.

Additionally, we have some really interesting data from Dr. Supriya Mohile at the University of Rochester looking at the use of a different type of assessment called the geriatric assessment for patients who are older. Now, we know that the geriatric assessment can identify patients who are at high risk for things like falls or cognitive changes or dementia, but what we don't necessarily know is whether if we routinely use the geriatric assessment, it helps us with our cancer treatment. And what they did in the study is they actually randomized patients to do the geriatric assessment. And in 1 arm, they showed the geriatric assessment to the oncologist, and in the other arm, they did not. And what they found is when they showed the geriatric assessment to the oncologist, the patient actually received treatment that was probably better for them based on the findings of their geriatric assessment. So patients who were more frail or who had more findings that would require an assessment and treatment had those things done. So if they needed a fall assessment, that got done. If they needed some neuropsych testing for their dementia, that got done. And for those patients, the oncologist often would choose to give a slightly lower dose of treatment to prevent further adverse effects. So what they found is that if you did a geriatric assessment routinely for older patients, you could appropriately provide for those needs and actually give them the treatment that is correct for them, preventing adverse events, preventing higher-grade toxicities, and ensuring that those patients got the best care.

And then finally, coming to our last group of trials, we had a really great discussion from Amber Barnato from the Dartmouth Research Institute. So it looked at variety of clinical trials of early palliative care integration as well as integrating palliative care through primary palliative care intervention. Now, what's the difference here? So primary palliative care intervention is when you teach clinicians, like your oncologist, to do palliative care themselves. So that's when they prescribe an opioid for pain, or that's when they do a goals of care discussion as part of routine advance care planning. Now, specialist palliative care interventions look a little different, and that's often when you have someone who's board-certified in palliative care and hospice, and they come in and do another consultation. And this would be akin to having a cardiologist come help your primary care doctor take care of your hypertension. This would be pulling in another team. So that's the difference between primary and specialist palliative care. So what we saw here is that there were 2 different types of interventions that were both really interesting.

Now 1 was done in University of Pennsylvania, where they actually looked at several thousands of patients who had their oncologists get a little nudge through an email that said, "You know what? Your patients coming in this week might be at a little bit of a higher risk for a poor outcome, at a higher risk for mortality. And when that happens, it might be good to do some advance care planning." So that these oncologists that got this email nudge, they were more likely to do the right thing by their patients. They were more likely to do an advance directive, and they were more likely to ensure that these patients had their goals of care documented and their prognosis documents within their charts. So something as simple as a mortality prediction done through a computational tool and an email to those oncologists could really improve getting the basics done for patients, such as getting their advance directive done.

Additionally, when we think about, now, specialist palliative care intervention, Dr. Barnato actually made a really beautiful point. She actually looked at a couple of different studies, 1 done by Tom Smith looking at integrating palliative care in phase 1 populations and the other by Dr. Areej El-Jawahri looking at integrating palliative care into the acute leukemia patient population. And both of these studies were really excellent studies that showed quality of life improvement with early integration of palliative care. And that is fantastic, and it supports the work that was led by Jennifer Temel in 2010, where she saw that if you integrated palliative care early and often, those patients had better quality of life, those caregivers did better, and those patients live longer.

And these studies continue to support the fact that early integration of palliative care improves quality of life for patients from a variety of different walks, whether it's phase 1 or acute leukemia. But what Amber Barnato pointed out was that palliative care also does something really different. What palliative care does is it also improves the way that we communicate across systems, and what she said, and I think it's important to point out, is that we don't often account for that in our metrics. We don't often point out that when a palliative care doctor talks to an oncologist, it decreases the anxiety of the oncologist. It makes the oncologist deliver better care. It actually changes the infrastructure of how we deliver care in the system, and that improves quality in ways that goes beyond the biopsychosocial model of just quality of life for patients but really changes the paradigm of how we deliver care across the system. And that we not only need to measure quality of life for patients but really look at some of these system changes that palliative care really helps to propagate and think about how that could be measured ongoing.

So it's been another great year for research. We're really excited about what our colleagues are doing out there in palliative care and supportive care and both in improving systems, improving risk assessments, and improving symptoms. We look forward to another year of research in ASCO 2021. Thank you so much for having me here today to talk to you a little bit about what we learned from our colleagues and friends.

ASCO: Thank you, Dr. Ramchandran. Learn more about the research presented at the ASCO20 Virtual Scientific Program at www.cancer.net/blog, and subscribe to Cancer.Net podcasts on Apple Podcasts or Google Play for additional episodes in the Research Round Up series, released throughout the summer.

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.

Brielle Gregory: Hi, everyone. I'm Brielle Gregory, 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 chemotherapy-induced peripheral neuropathy. Our guest is Dr. Charles Loprinzi. Dr. Loprinzi is the Regis Professor of Breast Cancer Research at the Mayo Clinic in Rochester, Minnesota, where he is an emeritus chair of the Division of Medical Oncology and an emeritus vice-chair of the Department of Oncology. He is also the Cancer.Net Associate Editor for Psychosocial Oncology. Thanks for joining us, Dr. Loprinzi.

Dr. Loprinzi: My pleasure to be here.

Brielle Gregory: Today, ASCO is publishing a new guideline on the prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers. Dr. Loprinzi served as the co-chair and lead author for this guideline. Before we begin, we should mention that Dr. Loprinzi has relationships to disclose related to this guideline. You can find his full disclosure statement on Cancer.Net. Now, let's talk a little bit about what this guideline means for people with cancer and those who care for them. So, Dr. Loprinzi, to get started, what is peripheral neuropathy?

Dr. Loprinzi: Peripheral neuropathy is pathology of nerves that's in the peripheral part of the body. But my English teacher in high school, a Catholic nun, would not like me to define a term with using the actual words there. So it's disease of the nerves—I'm going to use nerves instead of neuropathy—that's in the part of the body that's at the end of the extremities, the hands and the feet. It's caused by chemotherapy. Not all chemotherapy drugs cause neuropathy or pathology of the nerves, but some do. And that's what we're talking about today. And it is the symptoms that people get, numbness, tingling, and pain. Mostly numbness and tingling start, and then pain can come later on, but they're all three quite obviously.

Brielle Gregory: Thank you for explaining that. So why is this guideline on chemotherapy-induced peripheral neuropathy important for patients?

Dr. Loprinzi: It's important because it's a very prominent problem. It's very, very common. Again, not all chemotherapy drugs we give caused this particular problem, but some of them that we give-- and a good number of them that we give can cause this problem. And the problem can be bothersome while the patient's getting chemotherapy, and it can also last for a long time after chemotherapy is done. And that when I say a long time, that sometimes is months or years, and it could be a very prominent problem for some patients, a minority of patients there. There are some chemotherapy drugs like oxaliplatin, one of the drugs we give, that actually that neuropathy gets worse, the nerve problems get worse in the three months after stopping chemotherapy, and so you don't know the full extent of it for some time after you're done with the chemotherapy.

Brielle Gregory: That's really important to note. So when it comes to preventing chemotherapy-induced peripheral neuropathy, what does this guideline say about preventing chemotherapy-induced peripheral neuropathy?

Dr. Loprinzi: There have been a lot of studies that have looked at ways to try to prevent neuropathy. Unfortunately, there's no proven means of doing this, other than not giving the chemotherapy, and the reason for giving the chemotherapy is to try to kill off cancer cells so we don't like that part of it. And the drugs that we used that caused this neuropathy are some of the better drugs against the particular cancers that patients have. There is some suggestions that giving cold therapy, putting ice packs or cold gloves on hands and feet, with cold socks for the feet part of that. That can decrease the amount of blood flow and decrease the amount of nerve trouble that people get. It's not proof of benefit there. You always have to be somewhat careful, there have been occasional episodes of people who have gotten frostbite from that. But that's one of the things that looks like it might be doing some good. Again, more studies is needed.

Another way to try to decrease the blood flow is to put tight gloves on the hands, and therefore, the same sort of thing where you decrease the blood flow with cold therapy. There's some data that suggests that might be beneficial. And there are data that suggests that exercise could be beneficial. Patients who exercise more before and during chemotherapy seems to get less neuropathy than those patients who do not.

Brielle Gregory: All right. So let's move on to talking about treating chemotherapy-induced peripheral neuropathy. What does ASCO recommend in treating chemotherapy-induced peripheral neuropathy for patients who are currently receiving chemotherapy?

Dr. Loprinzi: So for patients who are getting chemotherapy, and for an example, when we're giving adjuvant chemotherapy which means that patients have had a surgical procedure and all known cancer has been removed, but we know based on the size of the cancer and whether it's involved lymph nodes and etc. things, even though we've removed everything we can see, we know that it comes back in a percentage of patients, in the future. And this is again from past experience. And the chance of the cancer coming back might be 10% chance or 20% chance or 50% chance or some other different number from that.

So we give 12 weeks of therapy to try to improve the chance that it won't come back. So that's the reason why we give the chemotherapy. But if a patient's getting neuropathy and fairly significant neuropathy, knowing it can get worse if you give more, and it gets worse even after you finish in many patients or in some patients. The doctor's role as per the guidelines is to think about how much additional benefit if I go from stopping at 8 cycles, if I go to the whole 12 cycles, how much additional benefit do we think that would decrease the cancer from coming back? Will that decrease it from coming back by 1 percentage point? Or will that be 5 percentage points? Or will that be 10 percentage points? Those are different numbers.

And then with that information, being able to share that with the patients and also share the neuropathy story and how much worse it might get depending on how badly it is getting so that decisions could be made. Should we stop short of what we were planning to do? Given that we do not want to have this neuropathy to be a problem that's around for months or years after finishing chemotherapy. So that's the one suggestion that was made by the guidelines. Having said that, there's no proof of any of this process that's the best way to go, but it's the best recommendation that we get.

Brielle Gregory: Now, what about for patients who have completed chemotherapy? What does ASCO recommend in treating chemotherapy-induced peripheral neuropathy for them?

Dr. Loprinzi: For those patients who have the problem after finishing chemotherapy, there is one drug that's around. It's a drug called duloxetine. It was developed as an antidepressant, but it also has been shown to be helpful in some pain situations. It's also been shown to be helpful in some pain situations. This drug is the one that in placebo-controlled trials, trials that randomized patients to get the drug or something that looked like it, just a sugar pill, if you will, that it does decrease pain and some tingling that patients get. It significantly decreases it. Having said that, it doesn't decrease it by a lot, and significant is a statistical term that says that this decrease did not happen by just chance alone.

So that's the one drug that's recommended in this particular situation. There are some things that look promising that you could argue would be worth trying, but do not have proof of benefit. And in that setting, we're trying to do more experiments to see if we can prove that these things are beneficial. And those three things are, one, acupuncture, two, exercise just like in the prevention mode, exercise seems to be helpful for decrease in the symptoms. And something else called scrambler therapy which is a type of nerve-stimulation therapy that's given on the skin of patients done by a machine in a doctor's office. So those are the three things that looked promising. Again, more work needs to be done to prove the true benefits and risks associated with these approaches.

Brielle Gregory: Great. This is definitely an important guideline for patients. So thank you so much for sharing your expertise today, Dr. Loprinzi, and for taking the time. It was such a pleasure having you.

Dr. Loprinzi: My pleasure.

ASCO: Thank you Dr. Loprinzi. 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 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. Sumanta (Monty) Pal, Dr. Petros Grivas, and Dr. Tian Zhang.

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

Dr. Pal is co-director of City of Hope's Kidney Cancer Program and is the head of the kidney and bladder cancer disease team at the institution. He has served in a consulting or advisory role for Astellas Pharma, Exelixis, and Pfizer.

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 Exelixis, Merck, and Pfizer.

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 Exelixis, Merck, and Pfizer.

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

Dr. Gilligan: Hi. I'm Dr. Timothy Gilligan from the Cleveland Clinic. I'm joined today by Dr. Monty Pal from the City of Hope Cancer Center, Dr. Petros Grivas from the Fred Hutchinson Cancer Research Center and University of Washington, and Dr. Tian Zhang from Duke Cancer Institute. Today, we're going to discuss three ongoing clinical trials in prostate, bladder, and kidney cancer. As you may know, clinical trials are the main way the doctors are able to find better treatment for cancer and other diseases. Patient participation is vital for clinical trials. By participating in a clinical trial, you can directly help researchers develop better treatment, reduce side effects, or even reduce the risk of cancer all together. The three trials we'll discuss today were chosen by members of the Cancer.Net Editorial Board Genitourinary Cancers Panel from the trials and progress abstracts that were presented at ASCO's 2020 Genitourinary Cancers Symposium. 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 visit the show notes for this episode on Cancer.Net.

So to get started, the first study we'll discuss is the TALAPRO-2 trial for prostate cancer, [Talazoparib + Enzalutamide vs. Enzalutamide Monotherapy in mCRPC (TALAPRO-2)] and Dr. Pal is going to discuss this. So if we could get started, just to begin with, who is the study designed for?

Dr. Pal: Thanks a lot, Dr. Gilligan. Well, this study addresses a unique disease population. It's patients with prostate cancer that's metastatic, and that implies that the cancer has migrated out of the prostate to other organs. But beyond that, it also implies that these patients have also developed some resistance to first line hormone treatment. So patients in this study [have] so-called hormone resistant or castration resistant [prostate cancer].

Dr. Gilligan: So if a patient was in this situation, and they weren't going on this trial, what would be the standard treatment for them at this time?

Dr. Pal: There are several options for these patients. Hormone therapies like abiraterone and enzalutamide could be considered. Chemotherapy is also a consideration.

Dr. Gilligan: And can you say a little bit more about what the patients would receive if they went on it? The subjects of the study, what they'll get?

Dr. Pal: Some patients with prostate cancer may have [a deficiency in their cancer's ability to repair damage to DNA]. This is something that we've seen in other tumor types, breast cancer perhaps being the most notable example. Pancreatic cancer being another one. In this particular trial, [the researchers] try to exploit that by using a class of drugs called PARP inhibitors. In this case, a drug called talazoparib. So patients in this study receive a standard hormone therapy called enzalutamide. And they receive that with or without this drug, talazoparib.

Dr. Gilligan: So they will get either-- what you described before is the standard of care—hormonal therapy, or that combined with this new drug.

Dr. Pal: That's exactly right, Dr. Gilligan.

Dr. Gilligan: I wanted to make that clear because this is a trial that has placebo, and sometimes research [participants] have concern about, "Do I want to be on a trial that has a placebo?" Do you want to say anything about that?

Dr. Pal: It's very important to bear in mind that every patient that enrolls in this study is going to get the standard treatment in this setting. As I've mentioned before, enzalutamide represents one of those options. And, of course, in this trial above and beyond that, they have the possibility of getting talazoparib or a placebo. So certainly patients won't be receiving placebo alone in this trial.

Dr. Gilligan: Do you want to say anything more about what's kind of interesting about this new approach to treating prostate cancer?

Dr. Pal: What I think is quite inventive about this study is that talazoparib, the PARP inhibitor, is being combined with hormone therapy. And I think that's the real difference in what this protocol offers versus the treatment strategies that now represent a standard option for patients.

Dr. Gilligan: Right. And my understanding is that the hope is that by using this combination, we'll be able to make treatment more effective.

Dr. Pal: Absolutely. When we talk about PARP inhibitors and prostate cancer currently, we're typically restricting it to patients who have these so-called DNA damage repair mutations. And that's certainly a finite group of individuals. In this particular trial, we're actually going to look not just at those patients, but all patients within this disease state. So we go beyond the 25 to 30 percent of patients who are estimated to have alterations in DNA damage repair.

Dr. Gilligan: Right. I think that's an important point: to get on this trial, patients don't have to have a particular genetic profile. So how will success be evaluated? How will we know if it's working?

Dr. Pal: In this case, we're going to be looking at the delay in cancer growth as the primary outcome measure. We're certainly hoping that the combination of enzalutamide with talazoparib is going to slow growth relative to enzalutamide plus placebo. The innovative endpoint that's explored in this study is also diving deeper and looking at those patients who have these DNA damage repair mutations that's going to also reflect one of the primary outcome measures in this study. And that's something quite important to bear in mind.

Dr. Gilligan: So we have some experience with PARP inhibitors. Can you say something about what we know about the side effects?

Dr. Pal: Fatigue is a relatively common side effect. Decreases in blood counts is another potential side effect. And in particular in my clinical experience, I've seen drops in the white blood cell counts. That of course makes patients more susceptible to infection. Diarrhea may also be one of the consequences within this class of drugs. And certainly, I would refer patients to a more comprehensive discussion of these side effects with their clinicians before entering into the study.

Dr. Gilligan: Is the trial still accruing patients? And do we know when we might expect results?

Dr. Pal: I think that there are many trials within this particular space. This one is ambitious in that it hopes to accrue over a thousand patients. I don't have a good finger on the pulse of when results will report. But I'm sure that'll be the subject of future podcasts for us.

Dr. Gilligan: Well, thank you very much Dr. Pal. It's a very exciting study and exciting new area of research in prostate cancer.

Dr. Pal: Definitely.

Dr. Gilligan: We're going to move on now to the second study we want to talk about, which is the KEYNOTE-905 study. [Perioperative Pembrolizumab (MK-3475) Plus Cystectomy or Perioperative Pembrolizumab Plus Enfortumab Vedotin Plus Cystectomy Versus Cystectomy Alone in Cisplatin-ineligible Participants With Muscle-invasive Bladder Cancer (MK-3475-905/KEYNOTE-905/EV-303)] And Dr. Grivas is going to talk to us about that. Can you orient us, Dr. Grivas, to what this study is, for which group of patients, and what it's looking at?

Dr. Grivas: This clinical trial is applicable to patients with localized, meaning not spread, bladder cancer. And when the bladder cancer has invaded the muscle layer of the bladder, we call this muscle invasive bladder cancer. And these patients usually go for cystectomy, the removal of the bladder. And ideally, they get chemotherapy before, but some patients may not be fit enough for chemotherapy. So those patients go straight to cystectomy, the removal of the bladder. So this clinical trial is trying to evaluate whether immunotherapy with this drug, called pembrolizumab, helps these patients before they get the cystectomy.

Dr. Gilligan: Can you tell us a little bit more about pembrolizumab and what we know about it? Where it's used currently in bladder cancer?

Dr. Grivas: Pembrolizumab has three different indications for patients with bladder cancer. The first one is in an earlier stage, what we call non-muscle invasive bladder cancer, which is a very superficial cancer, when the cancer is not invading through the muscle layer. And there's a specific indication for those patients who get therapy with BCG, which is a form of immunotherapy given inside the bladder. And if the cancer is not responding well to this BCG, usually, they go for removal of the bladder. But some of them may not be able to do that or do not want that. And pembrolizumab has a track record in those specific scenarios of BCG-unresponsive tumors as we call them for those patients who cannot get cystectomy or don't want to have it.

The other two indications are for patients who have metastatic, [meaning bladder cancer that has spread to other organs.] And there are two specific indications of pembrolizumab immunotherapy in that particular setting. So this trial is trying to expand upon the role of pembrolizumab in bladder cancer.

Dr. Gilligan: So it's been shown to be a benefit when the disease is more advanced and now we want to see if it's helpful earlier on in the period of time around surgery.

Dr. Grivas: Right. And it's interesting in a particular setting we're looking at this trial, because we have indications literally before and after in an earlier states, the non-muscle invasive disease setting. And also as you mentioned, Dr. Gilligan, in the more advanced setting. So we're trying now to see whether this middle setting of muscle invasive bladder cancer, whether there's a role of pembrolizumab by itself before removing the bladder.

Dr. Gilligan: Are patients who are eligible to get chemotherapy prior to cystectomy able to go on this trial or is it only for patients who are not [well enough] to get chemotherapy?

Dr. Grivas: This is for patients who are not in good condition to undergo chemotherapy. So if someone is in good condition to undergo chemotherapy, then the trial does not apply to them. This is only in those who cannot safely receive chemotherapy before the cystectomy.

Dr. Gilligan: Thank you for clarifying that. What data do we have that makes us think that it may be a good idea to give immunotherapy prior to cystectomy? Because this has been looked at a little bit already, and I think it's why this trial is being done. Can you say a little bit about that?

Dr. Grivas: Sure. I would like to underline that as you alluded before, the standard of care therapy for patients who undergo cystectomy, the removal of the bladder, is to undergo chemotherapy with a drug called cisplatin before cystectomy. But as we discussed before, this is the standard of care with a high evidence. However, many patients, maybe 50, maybe 55 percent of patients may not have enough condition to undergo this chemotherapy safely. And that is the population we would try to capture. And to answer your question, there have been so far, four clinical trials looking at immunotherapy before cystectomy. And all of those four clinical trials look very promising in that regard.

So based on this promising information, this new trial the KEYNOTE-905 is a phase III trial trying to confirm the promising data from the previous phase II trials and help us make a final decision whether this should be the standard of care or not in patients who cannot undergo safely chemotherapy in that setting.

Dr. Gilligan: What are the known side effects and risks of immunotherapy?

Dr. Grivas: Immunotherapy overall is much better tolerated than chemotherapy. However, it can still cause significant side effects, especially in a small proportion of patients. So the main thing we need to keep an eye on is if the immune system gets too overstimulated, it can cause what we call immunotherapy-related adverse events or side effects. And any organ of the body could in theory be attacked by an overstimulated, overactive, immune system. So they are different forms of "-itis." For example, if you have inflammation in the lungs, it's pneumonitis. In the liver, hepatitis. So we have to be careful and educate our patients, educate our medical providers and the teams, follow the patients and then report any new symptoms for changes in order to be able to recognize early and manage properly these side effects.

As I mentioned, it's not common to have a severe reaction, but it can happen. So education helps, and I recommend to the patients to discuss with a medical provider the potential of those immunotherapy-related adverse events that usually, if they occur, can be managed with proper treatment to try to suppress, "cool down," the immune system. So education is important.

Dr. Gilligan: So just to summarize then, this is a trial for patients who would normally be treated with surgery alone, and we're looking at whether adding immunotherapy before and after surgery can improve those outcomes.

Dr. Grivas: That's exactly right. Especially for those patients who cannot safely undergo chemotherapy before the surgery.

Dr. Gilligan: And how are we going to measure whether it's successful? Whether that immunotherapy has improved outcomes or not?

Dr. Grivas: The two measures that we're are looking at in this particular trial are the following. Number one, we tried to see how many patients--what is the proportion of patients from everybody who gets in the trial—who has no residual cancer cells at the time of the removal of the bladder, at the cystectomy. When the pathologist looks at the cystectomy sample in the lab after the bladder is removed from the body, what is the proportion of patients with no cancer inside the bladder after the immunotherapy compared to no immunotherapy at all? So we're going to compare these. We call this "complete response," meaning no cancer is found in the bladder after its been removed, after the immunotherapy. And we're going to compare this complete response in the two groups.

The other metric we use is to see how many patients have no recurrence regardless, meaning the cancer came back after the treatment. After the cystectomy, how many of those patients either had the cancer come back later or died from another cause. So we use these metrics and we compare the two metrics in the two populations in the trial with and without immunotherapy before the surgery.

Dr. Gilligan: And currently, the relapse rate's roughly 50 percent, so we're hoping for a lower number than that.

Dr. Grivas: Correct. We try to look for a lower number, and we try to see to compare these two populations with and without immunotherapy and see if immunotherapy adds value in that particular setting.

Dr. Gilligan: Is this trial still open and do you know when we might see results from it?

Dr. Grivas: The trial is open. It started recently, so I will strongly encourage the patients to discuss with their providers and look at particular locations where this trial is open. So definitely, there is room to go. And I think the trial will take a few years to complete and then report the results. So definitely an ongoing trial options for the patients.

Dr. Gilligan: Great. Well, thank you very much. So an exciting trial for patients with localized bladder cancer going through surgery to see if we can improve outcomes, increase the cure rate, by adding this interesting new immunotherapy. Thank you, Dr. Grivas.

Dr. Grivas: Thank you so much.

Dr. Gilligan: So now we're going to move on and talk about the COSMIC-313 trial with Dr. Zhang from the Duke Cancer Institute. [Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (COSMIC-313)] Can you tell us who this trial is designed for, or which group of patients?

Dr. Zhang: Absolutely. We know that for patients with kidney cancer with a clear cell component and intermediate or poor risk by IMDC criteria, that both immunotherapy combinations with ipilimumab and nivolumab as well as the targeted therapy blocking blood vessel formation, called cabozantinib, have both demonstrated significant benefit for these patients. And these are approved treatments. So this particular trial is attempting to combine these starting as a triplet of ipilimumab, nivolumab, cabozantinib for four cycles and then maintenance nivolumab with cabozantinib. And this triplet treatment is compared to a placebo-controlled regimen of the same immunotherapies without the targeted therapy.

Dr. Gilligan: So if a patient weren't going to go on this trial, what's the current standard of care?

Dr. Zhang: Both the immunotherapy combination as well as having the cabozantinib by itself, are our standard of care therapies for these patients in these categories.

Dr. Gilligan: Is this restricted to any particular group of kidney cancer patients?

Dr. Zhang: These patients must have at least one of the IMDC criterion. So these are markers of inflammation, like high neutrophil count, low hemoglobin, or high platelet levels, high calcium levels, as well as poor performance status in less than one year from diagnosis to needing these type of treatments. Patients have to have kidney cancer that spread to other sites of their body or locally advanced disease which is not surgically resectable. And as a note, other treatments that are approved in patients who have intermediate poor risk disease include combinations of immunotherapies with targeted therapies like pembrolizumab with axitinib or avelumab with axitinib.

Dr. Gilligan: So then just to be clear, these are drugs that are already being used, have already been shown to work, and we're trying to see if we combine them do we get a better result than using them by themselves.

Dr. Zhang: That's right. And I think that's a main point. If two agents work on their own, can they be combined to work better? It is important to note that we must follow these patients for their side effects to make sure that the benefit of the triplet therapy would be worth the potential added toxicity of this combination.

Dr. Gilligan: So as you mentioned, there's already a standard treatment that includes targeted therapies, immunotherapies, axitinib and pembrolizumab. What do you think is the interesting or different about the approach in this study?

Dr. Zhang: The main difference of this triplet combination is the addition of ipilimumab which is a CTLA 4 inhibitor. This is even a bit of a stronger immunotherapy, which targets the dendritic cell interaction with cells to activate the immune cells even more. And so we know that ipilimumab in kidney cancer does drive increase the ability for us to achieve a complete response, meaning that this combination is a really active immunotherapy combination for metastatic kidney cancer. So if we can add the ipilimumab effect with a very strong targeted effect of the cabozantinib the thought is that this triplet might be even more effective than the current standard of care, pembrolizumab-axitinib or avelumab-axitinib combinations.

Dr. Gilligan: Thank you for clarifying that. Just to make sure our listeners are clear on this. They're two doublets that are already approved—two kinds of immunotherapy or immunotherapy combined with targeted therapy. This will be the first triplet, if I understand correctly, that if this is shown to be more effective, it would be the first triplet therapy where we're using three different agents, our strongest immunotherapy combined with targeted therapy. Is that a fair summary?

Dr. Zhang: Absolutely. I think that's a great summary.

Dr. Gilligan: So how will success be evaluated? What are the endpoints for this?

Dr. Zhang: Success for this particular study will be evaluated by improving time until tumor growth and the safety of the triplet combination so the primary outcome of this particular study is improving progression free survival. But one of the key secondary endpoints, of course, is to make sure that the benefit of this triplet is worth the potential combined side effects. And then also to follow patients and see if it also improves survival to make patients live longer.

Dr. Gilligan: Do we have any sense of how long it'll be before we see outcomes from this? Or results?

Dr. Zhang: This is an ongoing international trial enrolling in the US but also spanning Europe, Asia, South America, Australia, and New Zealand sites. It will enroll up to 676 patients, and it's open currently. And patients should discuss it with their oncologist and see if it's open in a site close to them.

Dr. Gilligan: Dr. Grivas earlier told us about some of the side effects or risks with immunotherapy. This is combining immunotherapy with targeted therapy. Can you say a little bit about what we're gonna be watching for in terms of side effects or what we might expect?

Dr. Zhang: Sure. I think all of the immunotherapy side effects that Dr. Grivas told us about pertain to this study as well. The rashes, the diarrhea, inflammation of the lungs or liver, and affected endocrine dysfunction. But the targeted therapies can also have high blood pressure, rashes on the hand and feet, so called hand foot syndrome, also diarrhea, and elevation of liver enzymes, as well as the loss of protein in the urine. I think the one overlapping toxicity of cabozantinib with a combination of ipilimumab and nivolumab, the immunotherapy combination, is the diarrhea. So patients who start on this trial should be careful to report any diarrhea early on so that their oncologist and their investigators on the study can get an early handle and manage their diarrhea well.

Dr. Gilligan: Thank you. That's very helpful. One last question, I want to get back to that issue of eligibility. Sometimes when cancer patients want to go on a trial and they find that they are told they're not eligible to go on, this trial looking at intermediate risk patients specifically so a good risk patient might want to go on it and couldn't. Can you say a little bit about how those decisions are made and what the rationale for selecting groups of patients for trials is?

Dr. Zhang: Sure. We know that the IMDC criteria were really made in the setting of targeted therapies, and they were a set of prognostic markers and markers of inflammation, for example, and of time from initial diagnosis to treatment. But now they've been used often as stratification markers in our treatment trials and as selection now for eligibility. In particular for this patient population, ipilimumab, nivolumab seem to have more benefit in this intermediate and poor risk population. And so that's why, for this particular study, they're selecting specifically those patients with intermediate poor-risk disease.

Dr. Gilligan: So we want to focus on the patients who are most likely to benefit, it sounds like you're saying.

Dr. Zhang: That's right. So the favorable risk patient population do have a better prognosis in general, but those patients may not have as much benefit from the immunotherapy doublet.

Dr. Gilligan: All right. Thank you. Well, that brings us to the end of this podcast. Thanks for listening. 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. This is Timothy Gilligan. Thank you very much.

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

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.

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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 the data described here may change as research progresses.

Every year, the ASCO Annual Meeting brings together attendees from around the globe to learn about the latest research in the treatment and care of people with cancer. This year, a record 42,750 attendees from 138 countries worldwide gathered virtually for the ASCO20 Virtual Scientific Program, held Friday, May 29 through Sunday, May 31.

In the annual Research Round Up podcast series, Cancer.Net Associate Editors answer the question, "What was the most exciting or practice-changing research in your field presented at the ASCO20 Virtual Scientific Program?" In this first episode, 3 editors discuss new research in the fields of leukemia, colorectal cancer, and lung cancer.

First, Dr. Jessica Altman will discuss 2 studies in myelodysplastic syndromes and acute myeloid leukemia. Dr. Altman is Associate Professor of Medicine in the Hematology Oncology Division at the Feinberg School of Medicine, Northwestern Medicine. She is also the Cancer.Net Associate Editor for Leukemia.

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

Dr. Altman: Hi, everyone. My name is Jessica Altman. I am a leukemia physician at Northwestern Memorial Hospital in Chicago, and I am pleased to talk today about some interesting studies that were presented at ASCO 2020 and really use that as a marker of the excitement that is ongoing in the field of myeloid malignancies. In both myelodysplastic syndrome and acute myeloid leukemia, there have been a lot of novel therapies that have been recently approved, and other agents that are currently ongoing in a clinical trial. I think it's important for me to mention that the studies that I will be discussing today, I do not have any direct conflicts of interest, but I am involved with the development of other novel therapies. I'll be talking about two studies today. The first one is a clinical trial, and the second one is a palliative care study that was conducted.

The first study that I would like to discuss is the study presented in an oral session at this year's ASCO presented by Dr. David Sallman on behalf of his group at Moffitt and a large clinical trial network of other investigators. They studied the combination of a novel agent called magrolimab, which I'll mention more in a moment, in combination with a standard lower-intensity chemotherapy called azacitidine. This is studied for the treatment of high-risk myelodysplastic syndrome and acute myeloid leukemia. Magrolimab is an antibody that blocks something called PD47, which is a macrophage immune checkpoint and essentially a signaling cancer that says, "Don't eat me." And this antibody allows the engulfment or destruction of tumor cells and also is able to eliminate the really deep stem cells that cause the development or maintain the leukemia and MDS. So in this study, the investigators conducted a trial of azacitidine in combination with magrolimab, and they treated a handful of patients with both myelodysplastic syndrome and acute myeloid leukemia. And what they found was that the combination therapy was both well tolerated and resulted in a better-than-anticipated response rate. So better than what we would anticipate with a low-intensity chemotherapy alone. In particular, they found a nice response rate in individuals whose leukemia or MDS expresses a specific mutation. That mutation is called TP53, and that mutation has been associated with a poor chance of response to the available therapies and particularly a short duration of response.

This trial is particularly exciting to me because it demonstrates the ability to combine novel therapies with lower-intensity treatments and allows what we hope for will be a higher chance of response. This is with a relatively limited study, and further trials in this space involving this agent and combination are planned and are ongoing. There are other agents that are also targeting the TP53 mutation, and those are things to watch out for as well.

I'd like to move on to a supportive care study that was presented as well. This was a study that was presented by Dr. El-Jawahri, and funded by the Leukemia and Lymphoma Society. This is a study that looked at patients with acute myeloid leukemia receiving intensive chemotherapy. The relevance and importance for the study is because supportive care trials, and particularly looking at palliative care in general in acute myeloid leukemia have not frequently been done to date. And the background for this study is that individuals with acute myeloid leukemia frequently can experience decline in their quality of life and mood during their hospitalization for induction therapy. And it is not uncommon for adults with acute myeloid leukemia to receive aggressive care at the end of life.

So this group sought to examine the effect of an integrative palliative and oncology care and affect quality of life, mood and symptoms associated with things like post-traumatic stress and with a huge emphasis on end-of-life outcomes. And what this group found was that the integrative palliative and oncology care model for patients with acute myeloid leukemia receiving intensive chemotherapy led to improvements in patients' quality of life, their psychological distress and the care at the end of life. And the investigators asked for consideration of palliative care as a standard of care for all adults with acute myeloid leukemia, from really thinking about the incorporation of palliative care model, from diagnosis and throughout treatment and not just reserving that to the end of life.

Thank you for your time. I was very excited with the numerous clinical trials in the myeloid neoplasm space presented at this year's ASCO. And the work that was presented is really a marker of how much excitement there is that's ongoing in this field. Thank you.

ASCO: Thank you, Dr. Altman.

Next, Dr. Jeffrey Meyerhardt will discuss 4 studies in colorectal cancer. Dr. Meyerhardt is the Douglas Gray Woodruff Chair in Colorectal Cancer Research, Clinical Director and Senior Physician at the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute, Deputy Clinical Research Officer at the Dana-Farber Cancer Institute, and Professor of Medicine at Harvard Medical School. He is also the Cancer.Net Associate Editor for Gastrointestinal Cancers.

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

Dr. Meyerhardt: Hi my name's Jeff Meyerhardt from the Dana Farber Cancer Institute in Boston, Massachusetts. I'm going to speak about some of the key abstracts that were presented at this year's virtual ASCO meeting in 2020. I have no pertinent disclosures related to the abstracts I'm going to discuss. So the first and probably the most prominent and abstract, which was presented in the plenary session, was a study called KEYNOTE-177. It was a study specifically for patients with a certain subtype of metastatic colorectal cancer, what's called microsatellite unstable tumors. It's a way that colorectal cancers first emerged when they developed from normal cells to abnormal cells. It only constitutes about 3 to 5 percent of metastatic colorectal cancers. But we know a lot about those cancers because some of them are related to inherited conditions and some are not related to conditions, but they land up at those other cancers that seem to be much more susceptible to immunotherapy. And in fact, they're the ones that immunotherapy indicated for in terms of colorectal cancer.

And so the study that was presented was comparing patients receiving what's called a checkpoint inhibitor and a type of immunotherapy, in this case, pembrolizumab, to standard chemotherapy. So chemotherapy that we would typically give as initial treatment for metastatic colorectal cancer. Currently, the indication with the FDA is that patients would receive immunotherapy later as a later line of therapy, if other things weren't working and this was really to say, should we be giving it much earlier on?

So as a randomized trial, it was about 300 patients and they compared starting just with an immunotherapy, pembrolizumab versus chemotherapy and either a drug called bevacizumab or a type of a another inhibitor called an EGFR inhibitor, cetuximab. And it lands up starting with the pembrolizumab had a real significant improvement in progression free survival. It was a comparison of actually 8.2 months with standard treatments, which is what we see in a lot of trials versus 16.5 months. That's essentially for the times we had to switch to different therapy and all these other endpoints were also met in terms of a 12-month and two years of progression free survival. It was a statistically significant event, and it really will change practice for that subpopulation of patients with metastatic colorectal cancer. What's still really important is to try to figure out for the rest of the patients how immunotherapy can benefit them. And that unfortunately, we don't have as much data yet. Another abstract presented this year at ASCO was a sort of update of what's called the BEACON trial, and this is, again, another subgroup of colorectal cancers, colorectal cancers that have a particular mutation in them, what's called a BRAF mutation.

We know that occurs in somewhere between 5 and 10 percent of colorectal cancers. They can sometimes be a more aggressive cancer and there were multiple drugs that have been tested in multiple combinations of those drugs over the past 10 years, but the largest effort was really looking at trying to give patients a standard treatment to combining a BRAF inhibitor, in this case, encorafenib, which is an oral pill, with an EGFR inhibitor called cetuximab and also potentially adding a third drug, binimetinib, which is called a MEK inhibitor, also an oral pill. And the study, the BEACON study, which was a large international randomized study compared those three arms. The main comparison was saying, should you have two drugs compared to control or three drugs compared to control, control being standard treatment. And looking at both of those compared to standard treatments. They weren't actually meant to compare the two to three drug and initially the results suggest that three drugs was optimal. But the study that was presented at ASCO and ultimately actually led to the actual FDA approval, is using a two drug combination. So encorafenib and cetuximab, which again was better than control and really becomes the standard for later line treatment of BRAF mutated colorectal cancer. We don't know if that should be the initial treatment. That study is now about to get started to say, "Should we start with BRAF directed therapy?" but we know that if you had progressed in other standard treatment, that is certainly an option that should be considered.

There were two studies that looked at adjuvant therapy for colon cancer. Adjuvant is after someone has surgery and then they receive chemotherapy to reduce their risk of recurrence, one of them was a follow up to an effort to look at how many months of adjuvant therapy is necessary. This was called the IDEA collaboration. It was an international effort that included 14000 patients randomized to three months of treatment versus six months of treatment. And what we learned from that is for patients, particularly, who have a better risk tumor. So they all have stage III disease. Meaning they had surgery, the pathology showed some lymph nodes in the sample, but they didn't have evidence of metastatic disease at the time when they were diagnosed and those patients that they received three months of therapy if they only had one to three positive lymph nodes or not all the way through the bowel wall. Three months of therapy seemed to be just as good as six months, particularly when you do a combination of oral drug capecitabine with an IV medication called oxaliplatin and those with higher risk disease, those patients should probably receive six months, though in some cases, three months also seems to be sufficient. And this was a follow up to show that actually overall survival also was not inferior to do three months versus six months in those patients who have better risk disease or with capecitabine and oxaliplatin.

The second adjuvant trial was one that I actually led. It was a large trial that was run through the National Cancer Institute. It was looking at standard chemotherapy in stage III colon cancer, same population I just discussed, and whether adding celecoxib, which is what's called a Cox-2 inhibitors. It's kind of like aspirin, a little bit more specific. And then there was a lot of data that those type of drugs could be helpful in patients to reduce polyps and may potentially be beneficial in patients who already had colorectal cancer. So we conducted a large clinical trial, comparing standard chemotherapy with the celecoxib or standard chemotherapy alone. And unfortunately, adding the celecoxib didn't actually add any statistically significant benefit. There was a slight improvement, but it wasn't statistically significant. So it is a negative study and unfortunately does not move the field in terms of improving outcomes for patients with stage 3 colon cancer. There are still some ongoing studies, specifically looking at aspirin that we await to see if that would make a difference in outcomes. So those are some of the highlighted studies focused on colon and colorectal cancer from ASCO this year. Thank you very much. And again, my name's Jeff Meyerhardt from the Dana Farber Cancer Institute.

ASCO: Thank you, Dr. Meyerhardt.

Next, Dr. Jyoti Patel discusses 3 studies in non-small cell lung cancer. Dr. Patel is the Medical Director of Thoracic Oncology and Assistant Director for Clinical Research at the Lurie Cancer Center of Northwestern University. She also serves as Associate Vice Chair for Clinical Research in the Department of Medicine. She is also the Cancer.Net Associate Editor for Lung Cancer.

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

Dr. Patel: Hi. My name's Jyoti Patel. I'm a professor of medicine at Northwestern University and associate editor of Cancer.Net for lung cancer, and I'm going to talk about some of the most exciting lung cancer abstracts that were presented at the 2020 ASCO Annual Meeting. One of the most important and, I think, impactful to patients and practice-changing studies was actually selected as a plenary session abstract, and plenary abstracts are those that are rated the highest of all of the thousands of abstracts that are submitted, so whenever there's one in our particular disease site, we're always really excited, and we've been waiting for this ever since we heard from a press release that a positive study on lung cancer was going to be presented. The study was called the ADAURA study. And the ADAURA study was sponsored by AstraZeneca, and I have worked as a consultant for AstraZeneca in the past. So the study was looking at a drug called osimertinib, in patients who had early-stage lung cancer which was surgically resected. So as we know, a minority of patients, unfortunately, have stage I and stage II lung cancer, and about 30% of patients have stage III lung cancer. For many of these patients, surgery is the primary modality, and we do surgery with curative intent. However, despite doing surgery, there is a significant chance that the cancer can recur.

So the study was looking at osimertinib as adjuvant therapy in patients with resected lung cancer. Osimertinib is an EGFR tyrosine kinase inhibitor. It's a targeted therapy that blocks the EGFR protein, which is often mutated in patients with lung cancer. So osimertinib is the treatment of choice for patients with advanced lung cancer that harbor an EGFR mutation. That mutation occurs in about 15% of American patients, and higher proportions of patients in some parts of the world. These patients, early on, had surgery, and then they were found to have an EGFR mutation, and then they were randomized to either three years of osimertinib as a daily tablet, versus a placebo, and the endpoint of this study was disease-free survival, so that's the length of time until there's evidence that the cancer has recurred. In this study, taking osimertinib significantly reduced the chance that the cancer would return within those three years, and the magnitude of benefit was highly significant. So with higher stages of disease, the likelihood that the cancer could come back is higher, and so the benefit was greatest in patients with stage 2 and stage 3 disease, and in fact, in patients with stage 3 disease, it decreased the recurrence rate by almost 85%. So really, really significant and impactful to our patients.

Some people have questions about whether this should now be a standard of care, because we're not really showing whether we're improving the overall survival of patients. Many oncologists, myself included, think that survival with no evidence of disease is really meaningful for patients. It's going to be important, as the study matures, to see what the overall survival data look like, but in the three years of taking the drug, which is relatively well tolerated, the survival benefits, to me, translates to better quality of life, return to function and work, and staying away from catastrophic complications of cancer recurrence, like cancer coming back in the brain, or in the bone, and really impacting quality of life.

And the next study I want to discuss is a study looking at immunotherapy and chemotherapy in patients with non-small cell lung cancer. So the study is called 9LA. It's a CheckMate trial, so BMS studied their drugs nivolumab and ipilimumab in combination with chemotherapy. My institution has received research funding from BMS for the study of nivolumab and ipilimumab, and I've served as a consultant in the past. In this study, patients who were treatment-naive, so hadn't received prior therapy, were randomized to either chemotherapy, which was an older standard, admittedly, versus a combination of a short course of chemotherapy, so only for six weeks, in combination with the immunotherapies nivolumab and ipilimumab. The rationale for giving chemotherapy with immunotherapy is multifold. So one is that chemotherapy kills cancer cells, and in doing so, it releases neoantigens, or proteins, that might make the immunotherapy more effective. It sort of targets these cells as foreign, and it kind of helps amp up the immune system. It also sort of decreases the cancer burden, and we know that immunotherapy tends to be more effective when there's fewer sort of volumes of cancer to treat. So this was a really interesting design, and impactful because the chemotherapy is given for such a short course, so the ongoing toxicities of chemotherapy over several months, it sort of goes away. So less fatigue, less lowering of blood counts.

The study was looking at overall survival, and the study was positive, and this led to an FDA approval in May. The study showed that, in the initial time in which chemotherapy and immunotherapy were given, patients did quite well, and then they sort of plateaued, and at 12 months, almost two-thirds of patients were on the immunotherapy, compared to about half of patients which were on chemotherapy. And so that was significant. Although these results are comparable to other treatment options we have with ongoing chemotherapy and immunotherapy, are in patients with really high PDL numbers of immunotherapy alone, I think this trial is important for patients because it offers a different alternative. Having a short course of chemotherapy may make a lot of sense for patients. The cumulative toxicity from chemotherapy, it can't really be understated. Although our chemotherapies are better tolerated than ever before, the idea of just six weeks of chemotherapy and then going into immunotherapy, I think, is really an attractive one, and may give us options from multiple other treatments down the line. So I think this is important for patients. I think it certainly makes life a little bit more complicated for medical oncologists because now we have multiple options to discuss with patients, but at the end of the day, that's the best way we can personalize therapy for our patients, really taking into account overall disease status, as well as patient preferences, and tolerance of toxicities, and aims in the future.

The last study that I want to highlight is a study called the DESTINY study. I don't have any disclosures for this study. This study was looking at a subgroup of patients with lung adenocarcinoma with HER2 mutations. So there have been a lot of targeted therapies that have gained our attention and FDA approvals in the past couple of years, and it's really exciting. We're understanding that development of targeted therapies is based on early assessment of mutations in our patients, and we have a host of mutations, now, with FDA approved drugs. Just in May, drugs targeting RET, or R-E-T fusions was approved. Another drug targeting MET exon 14 skipping mutation was approved. HER2 mutations represent a subset of patients, a small subset of patients, about 2% of lung cancer patients, and they've been really difficult to treat. We know about HER2 because it's often a target for breast cancer, but in lung cancer, it's often a small mutation that causes activation, that causes the cells to grow. We haven't had a lot of really great options for these patients, and although there are multiple drugs in development, this particular trial gained a fair bit of attention because it looks quite promising.

So this study was looking at trastuzumab deruxtecan, and that's an antibody-drug conjugate. So the idea is it's an antibody that binds to HER2-- which is on cancer cells. When it binds to that target, the drug conjugate, or the payload, is released into the cancer cell. So there's less toxicity. It's a targeted therapy with very sort of directive toxin to the cancer cells. There are a number of antibody-drug conjugates in development, and some are FDA approved for other indications. In this study - it was a single-arm study - patients with HER2 mutations received the antibody-drug conjugate, and they saw a really significant response rate. Almost all patients had some disease diminution, some response, with about 60% of patients having what we call a partial response, a 30% reduction in tumor cells. What was also exciting was that some patients have been able to show that their responses are quite durable, and so the disease control has lasted. Certainly, this is an early trial. Only about 39 patients were treated. So we look forward to further studies of this compound, but finally, it's nice to have something that looks this promising in this particular patient population.

ASCO: Thank you, Dr. Patel. Learn more about the research presented at the ASCO20 Virtual Scientific Program at www.cancer.net/blog, and subscribe to Cancer.Net podcasts on Apple Podcasts or Google Play for additional episodes in the Research Round Up series, released throughout the summer.

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: Usted está escuchando un pódcast de Cancer.Net en español. Este sitio web de información sobre el cáncer es producido por la Sociedad Estadounidense de Oncología Clínica, o la American Society of Clinical Oncology en inglés, la organización profesional líder en el mundo para médicos que atienden a personas con cáncer.

El propósito de este pódcast es instruir y brindar información. Esto no es un sustituto de la atención médica profesional y no está previsto que sea utilizado para el diagnóstico o el tratamiento de afecciones individuales. Los invitados de este pódcast expresan sus opiniones, experiencias y conclusiones. La mención de cualquier producto, servicio, organización, actividad o terapia no debe considerarse como aval por parte de la American Society of Clinical Oncology. La investigación sobre el cáncer que se analiza en este pódcast está en curso; por lo tanto, los datos descritos aquí pueden variar a medida que la investigación avanza.

Leslie Zhang: Bienvenidos al podcast de Cancet.Net. Soy Leslie Zhang, una escritora médica para Cancet.Net. Como recordatorio, Cancet.Net es un sitio web de información para los pacientes por la sociedad estadounidense de un colegio clínico. Pueden encontrar más episodios del podcast en nuestro sitio: cancer.net/blog/podcast. En este episodio vamos a discutir los ensayos clínicos para encontrar nuevos tratamientos para el cáncer, y específicamente, la participación de los adultos mayores en los ensayos clínicos. Nuestro invitado hoy, es el doctor Enrique Soto, un oncólogo clínico que se especializa en el cuidado de los adultos mayores con cáncer. El doctor Soto, trabaja en el Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, en la ciudad de México y es un miembro de la Junta Directiva de la Sociedad Estadounidense de Oncología Clínica y un miembro de la Junta Editorial de Cancet.Net. Bienvenidos a podcast, otra vez, Dr. Soto.

Dr. Enrique Soto: ¡Hola, qué tal Leslie! Muchas gracias por invitarme nuevamente, es un gusto y un placer estar aquí.

Leslie Zhang: Bueno. Los ensayos clínicos son una parte importante en las investigaciones para encontrar tratamientos nuevos y maneras de prevenir el cáncer. Hoy hablamos sobre los beneficios y desafíos posibles que encuentran los adultos que tienen 65 años o más, cuando participan en un ensayo clínico. Doctor Soto, puede explicar con más detalles, ¿qué son los ensayos clínicos y por qué son tan importantes para las investigaciones oncológicas?

Dr. Enrique Soto: Claro Leslie. Entonces, un ensayo clínico es una evaluación experimental, es un experimento en el que se prueba la eficacia y la seguridad de un nuevo producto. Este producto puede ser una sustancia activa, un medicamento, una intervención, alguna cosa diagnóstica, como un nuevo estudio de imagen o un nuevo estudio de laboratorio y la idea de los ensayos clínicos, es demostrar que estas nuevas sustancias, estudios, intervenciones, funcionan para un desenlace particular. O sea, por ejemplo, que hacen que los pacientes con cáncer se curen más, vivan más tiempo, tengan una mejor calidad de vida y es muy importante realizar estos ensayos clínicos, porque es la única forma de estar seguros de que nuevas intervenciones son benéficas para nuestros pacientes y no les causan daño. Y hay muchos tipos de ensayo clínico, pero digamos, la forma más alta y de más alta evidencia de los ensayos clínicos, son los ensayos clínicos aleatorizados, que es lo que en inglés se llama "randomized clinical trials", que son el estándar de oro, o sea, el tipo de ensayo clínico más avanzado y en el cual, se comparan dos tratamientos distintos. Entonces, comparamos nuestro tratamiento nuevo o nuestra intervención nueva, ya sea con un tratamiento que tiene más tiempo o que es como lo que usa normalmente, o contra una cosa que se llama un placebo, que es un medicamento que no tiene sustancia activa, y comparamos nuestro medicamento nuevo contra este placebo y vemos si eso hace que las personas que entran en el estudio y que reciben este nuevo compuesto, vivan más tiempo, se curen más, tengan mejor calidad de vida. Y esto -evidentemente- es importantísimo, porque si le vamos a dar a la gente un tratamiento nuevo que potencialmente tiene costos, toxicidades, etcétera, queremos estar seguros que estos tratamientos hagan que las personas se sientan mejor o vivan más tiempo y que el medicamento o intervención nueva, sea lo más segura posible.

Leslie Zhang: ¿Y cuándo deben participar las personas en un ensayo clínico?

Dr. Enrique Soto: Bueno, creo que la mejor respuesta a eso es: Siempre. Lo ideal sería, que siempre las personas que reciben tratamientos para el cáncer, participen en algún ensayo clínico, porque esto ayuda a que se incremente el conocimiento y a que haya nuevas opciones de tratamiento; de hecho, casi todos los tratamientos que usamos hoy, al inicio, han sido utilizados en ensayos clínicos. Entonces -obviamente-, participar en ensayos clínicos, puede hacer que los pacientes tengan muchos beneficios, no solo para ellos, sino también para los demás. Entonces, participar en ensayos clínicos, ayuda a otras personas también. Desafortunadamente, esto no siempre es posible, porque no siempre hay ensayos clínicos para la enfermedad específica que tienen los pacientes y desafortunadamente, no todos los centros de cáncer en todo el mundo o en todos los lugares de Estados Unidos, tienen acceso a ensayos clínicos. Y, un tercer punto, es que no todos los pacientes -y esto es un problema para las personas mayores- cumplen los criterios que requiere tener una persona para entrar a un ensayo clínico. Todo los ensayos clínicos ponen una serie de criterios y las personas que cumplen esos criterios pueden participar y las que no los cumplen, no pueden participar. Y desafortunadamente, en muchos ensayos clínicos, los criterios discriminan contra las personas mayores, porque las cosas que ellos usan para definir quién entra, como por ejemplo, ciertos valores de laboratorio, son diferentes de las personas mayores y eso hace que sea más difícil para los adultos mayores entrar y es una de las cosas que tenemos que cambiar entre organizaciones como ASCO, los propios pacientes y los representantes de los pacientes, y también las compañías farmacéuticas y las instituciones que dan fondo para los estudios.

Leslie Zhang: ¿Y hay otras cosas que deben saber los adultos mayores acerca de los ensayos clínicos?

Dr. Enrique Soto: Sí, hay muchas cosas que deben de saber los adultos mayores para los ensayos clínicos. Primero que nada, deben de saber que los adultos mayores, no hay ninguna razón por la que no deben participar en ensayos clínicos. La otra cosa que deben saber, es que es importante preguntar sobre la disponibilidad de ensayos clínicos. Muchas veces, la principal razón para que las personas mayores no entren a los ensayos clínicos, es el sesgo y los prejuicios del médico que los está atendiendo. Muchas veces, es el propio médico el que dice: "Bueno, este paciente mayor, no le vamos a ofrecer participar en un ensayo clínico porque no va a querer, porque no se va a beneficiar, etcétera"; pero hay estudios muy interesantes que muestran que las personas mayores están tan dispuestas o más dispuestas que las personas jóvenes a participar en estudios de investigación. Entonces, creo que es muy importante que los adultos mayores sepan que estos estudios existen, que en muchos lugares están disponibles para ellos, pero que también necesitan preguntar por estos estudios y decirle a su médico si son candidatos a participar en alguno de ellos. Porque eso los puede beneficiar mucho, no solo a ellos, sino a los demás.

Leslie Zhang: ¿Y cómo pueden los adultos mayores encontrar ensayos clínicos apropiados para ellos?

Dr. Enrique Soto: Entonces, la primera forma y la más sencilla, es preguntarle a su médico qué ensayos están disponibles en el centro donde se están atendiendo. Pero también, hay muchos recursos para que las personas busquen ensayos clínicos, por ejemplo, Cancer.Net tiene una página específica en la que hay diferentes links a lugares donde se pueden buscar estudios. Hay diferentes páginas de organizaciones de pacientes y también de organizaciones de ensayos clínicos, que ofrecen esta información. Una de las más famosas es: clinicaltrials.gov y en esa página uno puede entrar, poner el tipo de enfermedad que tiene, el lugar del mundo en donde esté, ya sea el país en el que uno vive o el estado en el que uno vive -si es en los Estados Unidos-; y le pone una lista de los diferentes ensayos clínicos, los criterios de inclusión, etcétera, para cada uno de los estudios. Estas páginas pueden ser -en algunos casos- difíciles de navegar, pero como les menciono, en Cancer.Net vienen links a varios sitios, donde hay disponibilidad de recursos para ensayos clínicos.

Leslie Zhang: ¿Y hay otros desafíos específicos que los adultos mayores experimentan en la búsqueda para un ensayo clínico?

Dr. Enrique Soto: Sí. Desafortunadamente, las personas mayores se enfrentan a muchos desafíos cuando intentan entrar a un ensayo clínico. El primero -como ya les comenté-, es que puede que no estén disponibles en sus centros, muchas personas mayores se tratan en la comunidad, en los Estados Unidos, y en la comunidad -a veces- el acceso a los ensayos clínicos es mucho más limitado. El otro, es que los criterios de inclusión de los ensayos clínicos, pueden ser muy estrictos. Entonces, por ejemplo, la función del riñón o la función del hígado, que son cosas que se utilizan en los ensayos clínicos, pueden ser diferentes en los adultos mayores; y una persona mayor que está perfectamente bien, puede que no pueda entrar en un estudio, porque sus valores de función renal son más altos que el de la población joven, nada más por ser mayores, eso es un problema. Y de hecho, hay muchas iniciativas, ASCO tiene iniciativas junto con Friends of Cancer Research, para cambiar los criterios de inclusión y que las personas mayores puedan entrar de forma más fácil a los ensayos clínicos. El Instituto Nacional de Cáncer de los Estados Unidos, por ejemplo, ya está por ley, obligando a que los ensayos clínicos tengan una cantidad importante de adultos mayores, porque -obviamente- necesita ser representativo de la población. Pero todavía, los criterios de inclusión son una barrera para los adultos mayores. Otra cosa que puede ser una barrera para personas mayores, es la distancia que tienen que viajar para llegar a los centros que tienen ensayos clínicos y el número de visitas. Entonces, muchos ensayos clínicos se hacen en centros que están lejos de donde viven las personas mayores y requieren que se vaya muchas veces a estar haciendo estudios de imagen, estudios de laboratorio, etcétera; y para personas mayores que viven, por ejemplo, en asilos o que dependen de sus familiares para transportarse, esto puede ser una gran barrera que haga que no participen. Y eso es una de las cosas que nosotros, como médicos, tenemos que ayudar también, buscar formas para que los ensayos clínicos sean más accesibles para las personas mayores. Y otra, es esta idea errónea de que las personas que participan en los ensayos clínicos, son usados como conejillos de indias, que son usados como sujetos experimentales nada más y que no tienen derechos. Y es muy importante que la gente sepa, que participar en un ensayo clínico, no solo tiene como obligaciones, sino también, las personas que participan tienen derechos: su información tiene que ser respetada, todo el tiempo se debe de velar por la seguridad de los participantes y sí es importante que sepan, que eso es algo que se toma en cuenta cuando alguien participa en un ensayo clínico. Que esto sea seguro, para que una droga pueda evaluarse en un ensayo clínico, tiene que haber pasado por muchas cosas antes, para ver que sea segura.

Leslie Zhang: Perfecto, es información muy importante para los adultos mayores y para todas las personas que tienen cáncer también. ¿Hay alguna otra cosa que quiera explicar sobre los ensayos clínicos o específicamente para los adultos mayores?

Dr. Enrique Soto: Sí. Yo creo que una cosa muy importante, es que las personas mayores tienen que saber que, desafortunadamente, la mayoría de los medicamentos que utilizamos en cáncer, han sido probados -sobre todo- en gente joven. Y eso es, porque históricamente, las personas mayores, no participan en los ensayos clínicos. Desafortunadamente, muchas de las cosas que usamos para tratarlos, no están probados en ellos mismos. Entonces, es muy importante que las personas mayores participen en ensayos clínicos, para que se genere evidencia de lo que realmente beneficia a las personas mayores y lo que es útil y seguro para ellos. La única forma de que tengamos evidencia sólida de qué tratamientos se deben de dar en personas mayores, es que los adultos mayores participen en ensayos clínicos; y ese es nuestro trabajo como médicos, el trabajo de organizaciones como ASCO, pero también el trabajo de los pacientes y de las organizaciones de pacientes que deben de pelear para que los ensayos clínicos sean más incluyentes para las personas mayores, porque solo así vamos a poder avanzar.

Leslie Zhang: Perfecto. Muchas gracias por su participación en el podcast de Cancer.Net hoy, Dr. Soto.

Dr. Enrique Soto: Muchísimas gracias por invitarme, siempre es un gusto colaborar con Cancer.Net.

Leslie Zhang: Bueno, gracias.

Dr. Enrique Soto: Gracias Leslie [risas].

ASCO: Encuentre más información de confianza para personas con cáncer en www.cancer.net/es. Y si este pódcast fue útil, tómese un minuto para suscribirse, dar una calificación y escribir una reseña del programa en Apple Podcasts o Google Play.

Cancer.Net está respaldado por Conquer Cancer, la fundación de la American Society of Clinical Oncology que financia la investigación de vanguardia sobre todos los tipos de cáncer para ayudar a pacientes de todo el mundo. Para ayudar con la financiación de Cancer.Net y programas similares, haga su donación en conquer.org/support.

[music]

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

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. 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.

Greg Guthrie: Hi, everyone. I'm Greg Guthrie, 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 cachexia. And our guests are Dr. Charles Loprinzi and Hester Hill Schnipper. Dr. Loprinzi is the Regis Professor of Breast Cancer Research at the Mayo Clinic in Rochester Minnesota where he is an emeritus chair of the Division of Medical Oncology and an emeritus vice-chair of the Department of Oncology. He is also the Cancer.Net Associate Editor for Psychosocial Oncology. Thanks for joining us, Dr. Loprinzi.

Dr. Charles Loprinzi: It's good to be here, Greg.

Greg Guthrie: And Hester is the emeritus manager of oncology social work at Beth Israel Deaconess Medical Center in Boston. And she now works in private practice. A 2-time breast cancer survivor, she's a nationally known speaker, is active in numerous oncology organizations, and has written 2 books about breast cancer. Her daily clinical responsibilities include working with individuals, couples, and families living with cancer, and facilitating support groups. She is also a member of the Cancer.Net Editorial Board. Thanks for joining us today, Hester.

Hester Hill Schnipper: Thanks for inviting me.

Greg Guthrie: Great. Now, today, ASCO is publishing a new guideline on the management of cancer cachexia. Dr. Loprinzi and Hester both served on the panel for this guideline. Before we begin, we should mention that they do not have any relationships to disclose related to this guideline. But you can find their full disclosure statements on Cancer.Net. Now, let's talk a little bit about what this guideline means for people with cancer and those who care for them. So Dr. Loprinzi, what is cancer cachexia, and how common is it?

Dr. Charles Loprinzi: So cancer cachexia, the definition. We oftentimes call it cancer anorexia/cachexia, and so I'll try to define both anorexia and cachexia. A lot of people have heard of anorexia nervosa where people do not eat very well, so it's a loss of appetite is what anorexia is. For the cachexia part, you think of the people in the World War II camps when they came out at the end, where they had not eaten for a long time, and they were very, very, very thin. So cancer anorexia and cachexia is a phenomenon that comes on in patients with cancer, very frequently when they have advanced cancer, but oftentimes when they're just diagnosed, where patients are much thinner, and they're not eating very well.

Greg Guthrie: Hester, did you have something to add on that?

Hester Hill Schnipper: I think many patients, when they are newly diagnosed, experience appetite loss even if their weight has been normal up until then. But one of the ways to divide the world, are people who can't stop eating when they're under stress, and people who shut down and don't eat when they're under stress. So plenty of brand-new cancer patients fall into the second category, and, at least for some period of time during the particularly crisis anxiety-filled weeks around diagnosis, are not eating very much or very well. But that, generally, improves then as things settle down and their treatment begins and is not usually a cause for real worry.

Greg Guthrie: So is the cause of cancer cachexia often caused by the cancer itself, or is it a reaction to the cancer?

Hester Hill Schnipper: I suspect that Dr. Loprinzi can answer that better than I can. But my impression is that it usually is caused by the cancer itself and just the multiple medical problems that may accompany an advanced cancer.

Dr. Charles Loprinzi: So I agree with Hester on this point here. And it's not the treatment; it's the cancer itself. People used to think that patients who were receiving chemotherapy for early breast cancer, they were going to lose a lot of weight because patients who were getting chemotherapy for advanced disease lost a lot of weight. But in fact, patients with early breast cancer, when they get chemotherapy to try to help cure them, they gain weight. So it's not the chemotherapy that's causing the problem. It's the cancer itself. It changes the metabolic phenomenon of the body. People don't eat very well. And even if they get calories in, they don't metabolize them well, and so they still lose weight.

Greg Guthrie: So, Hester, what are some of the problems that can come from cachexia?

Hester Hill Schnipper: Well, certainly there are many medical related problems that Dr. Loprinzi can speak to better than I can. But the psychosocial or psychological issues also can be very troublesome for both the patient and those who love the person who is ill. If you are feeling terrible and not eating, that is obviously worrisome both to the patient and to their family members. And family members, generally, react by trying to encourage or even really pressure somebody to eat: making favorite foods, bringing in much more food than somebody wants, and then feeling very disappointed and perhaps even rejected if the patient just can't eat it. I mean, certainly, much of our advice—and maybe we're going to be talking a little bit more about this later—is to sort of back off and to a large extent let the patient direct what he or she is willing and able to eat.

Dr. Charles Loprinzi: And I would add to that, when you've lost a lot of weight and you're not eating well, it can impair your ability to function well. Patients who have lost weight, related to cancer, do worse in terms of prognosis, with shorter survival and more side effects from chemotherapy. And their quality of life is not as good. So it is a big problem with those situations.

Greg Guthrie: So who's generally bothered more by a patient's loss of appetite. Is it the patient or the patient's family and loved ones?

Hester Hill Schnipper: My experience is that it's generally more the family and loved ones. I mean, if the patient doesn't feel like eating, he or she just doesn't feel like eating. I mean, we've all had viral syndromes where, for a few days, we don't have any appetite. And you just don't have any appetite or are not interested in it. And I think some exaggerated version of that is probably what most patients feel. But family members feel very worried about it. There's all the sort of mythology around food and around nurturing and around love, and most of us take pleasure out of cooking for and feeding people whom we love. And when someone you love is sick, those feelings are even larger than they might otherwise be, and we kind of panic if everything we're trying to do to take care of somebody isn't working.

Dr. Charles Loprinzi: So I agree with Hester. In many patients, they just don't have an appetite. It's not a problem. It's not like they have pain, or it's not like they have nausea or vomiting. Now there are some patients whom that bothers them that they don't have an appetite, but many patients it really doesn't bother them. But as Hester said nicely, the family is oftentimes bothered tremendously by this particular situation.

Greg Guthrie: Okay. So, Hester, I'm going to follow up a little more. Is it important for family and loved ones to encourage patients to eat more then?

Hester Hill Schnipper: I think not. I think it is very important to try in a loving non-pressured way to communicate about it like, "Dad, is there anything you can think of that might taste good? Would you like a little bit of ice cream?" I mean, that kind of comment. And if dad says, "No. I don't want anything," then try again a few hours later.

I mean, certainly more frequent offerings of small amounts of food are much more likely to be accepted than bringing in a full dinner plate. But I think it's important to take cues from the patient because too much pressure is going to result in somebody eating even less than she might have otherwise.

Dr. Charles Loprinzi: I agree with that, 100%. There is actually an interesting story, true story, of a patient who mentioned this to somebody who was interviewing the patient afterwards. And the patient had advanced cancer and noted that when some of her relatives came in to visit her—and these are in her dying days and weeks—when her family came in to visit her, she would pretend she was asleep so she wouldn't have to interact with them because she knew they were just going to pressure to eat. And that's just a disaster in my mind. So it's a crazy sort of story to hear and all that. But I've mentioned that sometimes to patients' families so that they know don't over-bother the patients.

Hester Hill Schnipper: We can all relate to that. Even though you've always loved my lasagna, you may not want it tonight.

Dr. Charles Loprinzi: Yes. Especially if I have a viral syndrome and I just feel bad, I want to kick the food across the room because if I eat it, I'm going to throw up.

Hester Hill Schnipper: Right.

Greg Guthrie: So for patients who need nutrition, how often should tubes be inserted into the stomach to provide nutritional feedings?

Dr. Charles Loprinzi: So that's a great question, Greg. And there are ways you can get nutrition into a person who's not eating well, assuming their bowels are still working, and it's not a bowel obstruction sort of thing. And you can put food into the stomach. How can you do that? You can put a tube down their nose and put food in through that way—liquid nutrition that way. Or you can get a procedure done where you put a tube sticking out from the abdominal wall and the tube right into the stomach that way or to the small intestine. So you can give food in that manner. It's not infrequently done. Some countries more than others. And it's not frequently done.

It can be helpful on a patient who might have an obstruction of the esophagus so they can't otherwise swallow food, but, otherwise, the rest of the bowel is working and all that sort of thing. But oftentimes, if the bowel is working, if you put the food in that way, it does not improve quality of life or quantity of life for patients. And it can be a lot of hassle for doing it, and it's uncomfortable. So it's not recommended for most patients in this situation. If they just can't eat, then trying to force the food into them through their bowel does not seem to help things overall in terms of their quality or quantity of life. [crosstalk]

Hester Hill Schnipper: Yeah. My experience has been supporting everything you have just said, that this is a particularly difficult part of an ongoing difficult conversation between a doctor and a dying or very ill patient because most people think that if you don't eat, you're going to die more quickly. And families, particularly, often pressure the physician to go ahead in this way. And once you have put in a feeding tube or some other way to artificially feed someone, it's harder to take it out than it would have been to make the decision not to do it in the first place.

Greg Guthrie: So this is really an important quality of life decision?

Dr. Charles Loprinzi: Yes. You're right.

Hester Hill Schnipper: And the quality of life, obviously, being part of the bigger decision about quantity of life, and what are somebody's values and goals.

Greg Guthrie: So that's really interesting. We've talked about introducing nutrition directly to the bowel, but how often should intravenous nutrition be given to people with advanced cancer cachexia?

Dr. Charles Loprinzi: That's a great follow up question, Greg. So given intravenous or IV nutrition, that can be done. You can put an intravenous line oftentimes in the neck or sometimes in the thick part of the arm. And you can run nutrition in that way for days or weeks. So it can be done. It is done in patients who do not have functioning bowels, in general. And it could be helpful in that situation and could keep people alive for months and years in that situation.

In patients with advanced cancer where they're just not eating and they're losing weight, is it beneficial to do that in those patients where there's this metabolic problem, and even if you give nutrition to them, they don't use it very well, and they may not gain weight otherwise? So that's been the subject of a lot of randomized trials where half the people get the intravenous nutrition and half the people do not. And the data that are available are that those who get the intravenous nutrition do worse than the patients who do not. Part of that is because they can get infections from this process. Or part of it is that you can get the glucose too high. And it's a lot of a hassle that sort of way. There's even some situations where cancers might grow faster by giving them more nutrition there.

So it's not recommended to be done in most patients. Sometimes, it is started. And if it is started, there should be clear goals, "Okay. We're going to do this for a month, and our goal is this so that mom gets strong enough to walk to the mailbox," and if at one month, she's doing worse and not doing that then it's oftentimes time to say, "Okay. Let's stop that. It didn't work very well."

Greg Guthrie: So Dr. Loprinzi, we've talked about nutrition, but how is cancer cachexia treated?

Dr. Charles Loprinzi: That's a good question. We've actually started off with a lot of the things you can't do. But what can you do? And those are somewhat limited, unfortunately. But there are some things. One is nutritional consultation, dietitian, that sort of thing. Part of the benefit they can provide is to recommend patients don't take crazy diets. And there are a lot of crazy diets out there recommended for patients with cancer. And they might be able to help them so that they can get more nutrition in. There's not a lot of randomized data to demonstrate that does a lot of good, but it's a recommendation that makes some sense.

On the other hand, what about giving drugs? There are many drugs that have been studied, randomized controlled trials with placebo where half the people get the drug and half the people get a placebo. And there are 10 or 15 things that have been tried. There are a couple of them that do show that you can use the drugs to stimulate appetite and improve weight. And there are 2 different classes of drugs. One is a steroid medication like dexamethasone. And the other is a progesterone hormone-like medication like megestrol acetate. So those can be given.

The guidelines that ASCO came out with recently that looked at this, and looked at all the randomized trials, suggested that physicians should not feel pressured to give these medications. And the reason for that is that these medications do not improve quality of life or survival, and they can have some side effects. Steroid medications can increase the chance of infection. They can cause peptic ulcer disease or stomach ulcer disease. The megestrol acetate can cause blood clots. And in some of the randomized trials, the patients who got the megestrol acetate for treating cachexia, on average, died sooner than the patients who did not. So not recommended for everybody. But if a patient really says, "My loss of appetite is really bothering me, not the family, but bothering me," then they might choose to try these medications. It's reasonable to try them for a limited period of time and then see if they work, right? For 2 weeks or 3 weeks, and then stop if it doesn't work. There are studies going on trying to find newer better agents for this situation, but results from those are not available yet.

Greg Guthrie: Great. So, Hester, how does this ASCO guideline, management of cancer cachexia, help improve the lives of patients?

Hester Hill Schnipper: Well, we're hoping that this ASCO guideline, like all the others, will be useful to physicians, nurses, dieticians, patients, and families themselves, anybody working with cancer patients or thinking about how to improve the quality of life of cancer patients. I am particularly hoping that these guidelines will decrease the use of very difficult treatments that don't generally help or improve somebody's quality of life or the length of time that someone has to live in very difficult and stressful circumstances. We're hoping that it will help families understand why medical recommendations are made and why, often, in this situation, the recommendation is to not do something, because that's not usually what families expect to hear. So understanding better that the focus needs to be on someone's quality of life and how best to make the best of whatever days there are, that's one of our major goals. I also would like to add that I regularly write a blog called Living With Cancer which is published through the BIDMC Cancer Center, and there is a blog available talking more about this issue and primarily from the psychosocial or family side of it.

Greg Guthrie: Thanks for sharing that, Hester. We'll definitely put a link to that in our blog post on this podcast and in the transcript. But this has been a really helpful discussion. It's really important to talk about cachexia in terms of quality of life. And, obviously, this is an important facet for this ASCO guideline to cover. So Dr. Loprinzi, Hester, thank you for sharing your expertise and insight today. It was great having you.

Hester Hill Schnipper: Thank you so very much for asking me.

Dr. Charles Loprinzi: Thank you very much.

ASCO: Learn more about cancer cachexia at www.cancer.net/appetiteloss and www.cancer.net/weightloss. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

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