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In this episode of the ASCO eLearning Podcast, Gregory Masters, MD, and Christina Dieli-Conwright, PhD, MpH, dive into the exciting benefits of exercise for patients with early-stage cancer, advanced disease, and how exercise could preemptively lower risk. To hear the latest eLearning Podcast episodes as soon as they are available, please subscribe on Apple Podcasts. To access our entire library of podcasts and other amazing eLearning content, visit elearning.asco.org. TRANSCRIPT CLIFFORD HUDIS: Hello, I'm Dr. Clifford Hudis, CEO of ASCO, dropping into your feed to let you know about a special episode of the ASCO in Action podcast featuring the extraordinary career of Dr. Richard Schilsky, ASCO's chief medical officer. Rich and I discuss the advances that have revolutionized cancer care over the last 50 years and much, much more. Here's a preview of the episode. RICHARD SCHILSKY: The 1980s, in many respects, were the doldrums of progress in clinical oncology. There really was not a lot of innovation in the clinic. But what was happening and what was invisible to many of us, of course, was that was the decade of discovery of the fundamental biology of cancer. That's when oncogenes were discovered, when tumor suppressor genes were discovered, when it became clear that cancer was really a genetic disease. And that is what transformed the field and put us on the path to targeted therapy and precision medicine as we think of it today. CLIFFORD HUDIS: You can find the ASCO in Action podcast on Apple Podcasts or wherever you are listening to this show. And you can find all nine of ASCO's podcasts, which cover a wide range of educational and scientific content and offer enriching insight into the world of cancer care at podcast.asco.org. SPEAKER: The purpose of this podcast is to educate and inform. This is not a substitute for 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. GREGORY MASTERS: Hello, I'm Dr. Gregory Masters. I'm a medical oncologist at the Helen F Graham Cancer Center in Delaware. CHRISTINA DIELI-CONWRIGHT: And my name is Christina Dieli-Conwright. And I'm a member of the faculty at the Dana-Farber Cancer Institute in the division of population sciences and department of medical oncology. GREGORY MASTERS: We would like to discuss the role that exercise and physical activity can play in providing excellent cancer care to your patients. And we'll start with a brief case presentation to review how exercise can improve the care in patients with early-stage cancer. The first patient is a 51-year-old postmenopausal female who presented with stage IB hormone receptor positive, HER2 negative breast cancer. Sentinel lymph node biopsy was negative. And she underwent lumpectomy, followed by radiation therapy. She had a low recurrence score on the 21-gene expression assay and saw a medical oncologist to consider additional therapy. She agreed to take anastrozole off for five years. At the end of the office visit, she poses the question, besides surgery, radiation, and hormonal therapy, what else can I do to improve my chances? CHRISTINA DIELI-CONWRIGHT: What is the role for exercise in patients with early-stage cancer? GREGORY MASTERS: Well, Christina, it's important to understand that exercise can help improve and maintain a healthy lifestyle in most patients, regardless of a cancer diagnosis. But there's a particular benefit in cancer patients and, also, in helping to reduce the risk of cancer as well. Studies show a decreased risk of getting certain cancer in patients who exercise on a regular basis. There's a decreased risk of developing cancer of the breast, colon, endometrium, kidney, bladder, esophagus, and stomach. The hazard ratio is 0.6 to 0.9 for developing these cancers. That is, there's a 10% to 40% reduction in the risk of getting one of these cancers. The evidence is convincing, with both statistically and clinically significant reductions in developing cancer. There's also evidence that sitting time or complete inactivity may increase the risk of cancer. Multiple types of exercise can help, including both recreational or leisure time exercise and occupational physical activity. Those who are very active at work may achieve a similar benefit. CHRISTINA DIELI-CONWRIGHT: How does this affect quality of life and cancer outcomes? GREGORY MASTERS: So exercise can help reduce the risk of developing cancer. But exercise also improves health in patients who are being treated or have been treated for early-stage cancer. Physical activity has been correlated with improved cancer-specific and all-cause mortality. That means physically active patients are less likely to die of their cancer or other causes. A hazard ratio for death is 0.67 to 0.7 for breast, cancer, and colorectal cancer patients. That means there's a 30% reduction in the risk of death in those who exercise regularly. This holds for both prediagnosis exercise and postdiagnosis exercise. So patients who are already in an exercise routine when diagnosed and those who begin an exercise program after their cancer diagnosis can achieve benefits from exercise. There appears to be a dose-response relationship. So the more one exercises, the better, within reasonable guidelines. The American Cancer Society estimates that about 15 million cancer survivors alive in the United States may benefit from exercise. But there are some limitations to these studies. There may be patient recall bias, meaning that some patients may overestimate their activity to please questioners. These data also come from nonrandomized studies for the most part. So other factors, such as a healthy lifestyle, may also be at play. Some studies compare the highest to the lowest risk groups to calculate the risk ratio. So the data may overestimate risk reduction in some patient groups. Another benefit is that symptoms can improve with exercise, leading to a better overall quality of life. Studies have shown an improvement in fatigue, physical functioning, and physical fitness, and a reduction in depression and anxiety. And of course, the added benefit comes that overall cardiovascular risk may be reduced with exercise. CHRISTINA DIELI-CONWRIGHT: Is it safe to exercise during chemotherapy and/or radiation therapy? GREGORY MASTERS: Exercise is safe in the cancer population. In studies looking at adverse events in patients enrolling in a postdiagnosis physical activity program do not show unexpected safety concerns. Nonetheless, there remain major challenges in implementing these recommendations in the broad cancer patient population. One problem can be getting providers to adopt the recommendations. Another issue is time constraints for both patients and health care providers. There may be knowledge deficits in providers. And although 79% of oncologists agree that referral to an exercise program is important, in one ASCO survey, only 10% to 20% of providers actively refer patients to these programs. One strategy for getting providers and their patients engaged may be to assess, advise, and refer. This is one way to support providers in the steps needed to boost participation. There can also be constraints from a patient-care side. Getting patients to follow through on our recommendations can be a challenge. And we need to focus on behavioral changes. Patients need a strong support system, including not only their oncologist, but also family and caregivers, oncology, nurses, physical therapists, occupational therapists, and trainers to help them with their routines. Specific programs can be helpful, such as Livestrong at the YMCA. A patient's access to this care can be limited for various reasons, socioeconomic or otherwise. But we know that cost, insurance coverage, and time out of work can be a challenge. It may be difficult for these patients to commit more time and effort to an exercise routine after going through extensive treatment. And we know there's a dire need to reach underserved populations. This is a perfect time to remember the focus of Dr. Lori Pierce, the current ASCO president, who has as her theme, equity, every patient, every day, everywhere. Remember, we can all work together to help our patients strive for their best health through exercise. And for our early-stage breast cancer patient, to help her improve her chances, in addition to standard care, I would recommend a regular exercise routine, perhaps with referral to a specialist in exercise physiology. CHRISTINA DIELI-CONWRIGHT: Greg, are there specific clinical concerns to address? GREGORY MASTERS: As a medical oncologist, before I refer a patient for exercise, I consider comorbid medical conditions, such as cardiac, pulmonary, orthopedic, central nervous system, and neurologic complaints, and any post-operative limitations that may be appropriate. Thank you. CHRISTINA DIELI-CONWRIGHT: I have the pleasure of discussing a second case with you today. And this case is a 60-year-old male who underwent surgery five years ago for stage II colon cancer. Earlier this year, his CA tumor marker was elevated. And a CT scan showed new metastatic disease in the liver and lung. Biopsy confirmed metastatic adenocarcinoma. Molecular testing shows the cancer is KRAS mutation positive. Symptoms include fatigue, anorexia, and mild cough. And he still gets occasional diarrhea since surgery. He begins chemotherapy with FOLFOX and bevacizumab. At the next visit, he has increased complaints about his energy level and mild depression. He asks, besides chemotherapy, what more can I do to improve my quality of life? So I'm here to share with you today the role of exercise and its benefits in a case just like this, with patients with metastatic cancer. GREGORY MASTERS: What is the role for exercise in patients with advanced cancers? And how does it affect their quality of life, symptom management, and prognosis? CHRISTINA DIELI-CONWRIGHT: So this is a very interesting question, given that very few studies, intervention studies specifically with exercise, that have actually targeted specifically patients with metastatic disease. However, there are pilot studies that have smaller patients enrolled that have shown that exercise is feasible and safe for patients with metastatic disease. And to date, exercise in patients with metastatic disease, although few, have shown to improve quality of life and physical function. And by physical function, I'm referring to how quickly an individual is actually able to walk and the distance by which they're able to walk over a certain period of time. So importantly, we need to emphasize that research is actually heavily lacking in this population. So further and ongoing research that has yet to be published is underway and needed to determine whether exercise can impact symptom management and also improve prognosis in patients with metastatic disease. GREGORY MASTERS: What safety precautions should a patient be aware of when performing exercise? CHRISTINA DIELI-CONWRIGHT: So it is advised to have an understanding of one's own physical personal strengths and weaknesses as well as prior medical history before initiating exercise. And perhaps this is even more important in an individual with a metastatic diagnosis. Importantly, consideration of daily aches and pains, overall well-being, time since last exercise was performed regularly are important, but just a few examples of considerations to understand. This basic information will really help to determine which forms of exercise are safe and which forms of exercise should be future recommended. Consulting with a medical oncologist prior to starting an exercise program is advised. And subsequently, that physician may also refer that patient to see a professional exercise specialist. In line with this recommendation, there actually are specialized exercise professionals with unique training in exercise for cancer patients, who can assist in providing personalized exercise guidance for patients with cancer. And it is possible to seek out those recommendations using a website provided by the American College of Sports Medicine. GREGORY MASTERS: Will exercise during treatment aid in how well a patient tolerates treatment? CHRISTINA DIELI-CONWRIGHT: Exercise during treatment may aid in how well a patient tolerates treatment. However, there is no scientific evidence yet to support this, specifically within the metastatic population. Logically, we do know that exercise during treatment has many physical health benefits, such as maintaining strength and physical endurance. And that may help to keep the patient fit so that they're able to better withstand the treatment as opposed to if they were not fit. However, studies are underway to help to continue to support this logic. GREGORY MASTERS: What are the best ways to help patients understand this information and to get them to initiate and stick with an exercise routine? CHRISTINA DIELI-CONWRIGHT: So this is a fantastic question and this is a question that highlights the challenges of individuals difficulties adhering to regular exercise, in general, throughout the lifetime. However, there are some great resources specific to individuals diagnosed with cancer that are worth mentioning. For example, website and organization referred to as cancer.net offers a number of brief articles focused on exercise that provide great readings around the benefits of exercise before, during, and after treatment, et cetera. Often the easiest way to get started and to stick with exercise is to start with an enjoyable activity that will be based on one's personal preference and to start small. It's not necessary to choose an activity that is completely unenjoyable or for an excess amount of time because then that will often result in a person not adhering to what they're trying to achieve. Exercise can often appear very daunting when it's examined in a very high volume or at a very high intensity if that's the only way that it's thought to be able to be performed. So starting simple by taking short walking breaks to reduce sitting time can actually go a long way. And there's more and more research to support the benefits of reducing sitting behavior. Individuals are also more likely to stick with an activity when they enjoy the activity and when it is not too time consuming. Another tidbit is exercising with family, friends, or in a group setting when it's safe can also promote consistency with exercise. Nowadays, there are a lot of virtual exercise programs in light of the COVID pandemic that actually can involve exercising in a group with family or with friends but being socially distant via virtual platform. Also important to note, when approaching more advanced forms of exercise, such as weightlifting or training for a specific event, such as a running event like a half marathon or a 3K, 5K, it is definitely helpful to seek professional assistance, even if for a single consultation. This way you're on a straight and clear path of how to safely go about performing the exercise. And specifically, with our patient diagnosed with metastatic disease, exercise is safe and feasible. However, relying on consultations by medical oncologists and also exercise professionals will really help to put that individual in safe hands to get off on a safe start in order to perform the exercise and help to benefit the improvements of quality of life and strength and physical function that we know are well-established among cancer survivors. Thank you so much for your time. GREGORY MASTERS: Now that we have reviewed these two cases, let's consider how these cases are related. There's evidence that exercise benefits patients with both early-stage cancer and advanced disease. There's also evidence that exercise can help reduce the risk of cancer prior to diagnosis. Based on these studies, there's strong evidence supporting our recommendations to patients that they become more active. Beyond understanding the data, sometimes the hardest component of this is getting patients to implement our recommendations. The take-home point should be that exercise helps both groups of patients and that we should be recommending exercise for this patient population. CHRISTINA DIELI-CONWRIGHT: The key teaching points from our session today should be recommending exercise for patients with early-stage or advanced cancer is evidence-based and will improve multiple health outcomes. The goals, therefore, are coming up with the best way to teach our patients this information and helping them to act on that knowledge. Barriers may include lack of energy, which limits patients initial interest to pursue exercise as therapy. GREGORY MASTERS: Thank you for listening to this week's episode of the ASCO eLearning Podcast. SPEAKER: To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive eLearning center at elearning.asco.org.

Dr. Stephen Hunger is a Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. In today's ASCO eLearning Podcast, Dr. Hunger will discuss two patient cases related to CAR T-cell therapy. While the two cases are similar, the recommended treatments can be different. We hope you enjoy this episode. To hear the latest eLearning Podcast episodes as soon as they are available, please subscribe on Apple Podcasts or Google Play. We truly value your feedback, so please leave a review. To access our entire library of podcasts and other amazing eLearning content, visit elearning.asco.org. Transcription: The purpose of this podcast is to educate and inform. This is not a substitute for 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. Hi, my name is Stephen Hunger. I'm a professor of pediatrics in the Perelman School of Medicine at the University of Pennsylvania, and chief of the Division of Oncology and director of the Center for Childhood Cancer Research at the Children's Hospital of Philadelphia. My career has focused on clinical, translational, and basic research regarding childhood Acute Lymphoblastic Leukemia, or ALL. One of the most exciting recent advances in cancer medicine is the development of Chimeric Antigen Receptor-redirected, or CAR-T cell therapy for relapsed in refractory pediatric B cell ALL. Today, I will present two cases that have similarities, but also important differences that highlight key questions and uncertainties regarding when and how to use CAR T cells in pediatric ALL. Currently the only CAR T cell product FDA approved for treatment of children and young adults up to age 25 with relapsed refractory ALL is tisagenlecleucel, trade name Kymriah. Additional CAR T cell products are in the late stages of testing, and will likely become FDA approved soon. My discussion today will focus on tisagenlecleucel, which can persist for years following therapy. Indeed, the first child treated at CHOP for ALL with CAR T cells in 2012 still has detectable CAR T cells over eight years later. Our first patient is Sue, who is currently 15 years old and has B-ALL that relapsed for the second time. She was first diagnosed at age 7, at which time she had an 80,000 white blood cell count. She was treated with standard chemotherapy with an excellent response, but relapsed during maintenance therapy 22 months following her diagnosis. Because this relapse occurred on therapy, she was considered high risk, and allogeneic transplant was considered the therapy of choice. She entered a second remission and became MRD negative after two cycles of consolidation therapy. Her brother was HLA identical, and she underwent a matched sibling transplant in MRD negative second remission following a cyclophosphamide mind plus total body radiation preparative regimen. She engrafted rapidly, had no GBHD, and was weaned off immunosuppression by six months post-transplant. One year post-transplant, she presented with bone pain and was found to have a second bone marrow relapse of B-ALL. Her leukemia cells were CD19 positive. Our second patient is 15-year-old Damian, who was diagnosed with CD19 positive B cell ALL four months ago. His initial white blood cell count was 80,000, and the cytogenetic and molecular studies did not show any known high or low-risk features or targetable lesions. He was treated with standard chemotherapy, but did not enter remission with 50% blasts at the end of four weeks of induction therapy. He received one month of consolidation chemotherapy with a Children's Oncology Group augmented BFM regimen, but still had 35% blasts after that therapy. He then received a four-week course of the CD3/CD19 BiTE blinatumomab, but again had 30% blasts at the end of that therapy. The blasts remained strongly CD19 positive. His 17-year-old sister is fully HLA matched. Both of these patients have relapsed refractory ALL, and meet the FDA approved indication for tisagenlecleucel, which is patients up to 25 years of age with B cell precursor ALL that is refractory or in second or later relapse. Sue is in her second relapse, and thus qualifies. Refractory is not defined precisely in the indication, but I think all would classify Damian as having refractory ALL, given that he has failed to enter remission with three different regimens. The pivotal trial that led to the approval of tisagenlecleucel was called ELIANA, and the results were published in the New England Journal of Medicine in 2018, with my colleague Shannon Maude being the first author. Of note, that study prohibited patients who had received prior CD19-directed therapy, so Damian would not have been eligible to enroll. However, the FDA label does not mention this, and many patients have been treated with tisagenlecleucel following earlier blinatumomab therapy. Thus, Sue and Damian are good candidates for tisagenlecleucel. Both are also medically in good condition without active infection or end organ dysfunction. There are also important differences between Sue and Damien. Sue has relapsed post-transplant while Damien has an HLA-matched sibling, but has never undergone transplant because he has never entered remission. Transplant with high level marrow disease, as he has currently, 30% blasts, is generally viewed futile, and the best transplant outcomes occur when patients are MRD negative immediately pre-transplant. A key current question in therapy of relapsed refractory ALL is whether CAR T cells should be used as a definitive therapy with responders receiving no subsequent antileukemia treatment, or as a so-called bridge to transplant, a means to get patients to an MRD negative state so that they can then undergo transplant as definitive therapy. There is no current definitive answer to this question, and these two cases help to highlight the issues to consider. Both Sue and Damian undergo T cell apheresis with a good collection. Cells are sent to the manufacturer to make the CAR T cells, a process that takes about four weeks. They receive low-intensity maintenance therapy for two weeks with adequate disease control, and then no therapy is given for two weeks. Both have adequate manufacture of CAR T cells, and then receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by CAR T cell infusion. Both patients have mild signs of cytokine release syndrome not requiring intervention. At day 30 post-infusion, both Sue and Damian are in an MRD negative complete remission and have no detectable circulating B cells. What should happen next? While some feel that the long-term efficacy of CAR T cells have not yet been established, and that transplant should be used as a consolidative therapy in almost all cases, many others believe that a long-lasting CAR T cell product such as tisagenlecleucel can be used as definitive therapy in some cases. In the initial ELIANA publication, 81% of the 75 relapsed refractory ALL patients infused with tisagenlecleucel obtained in MRD negative complete remission within three months, usually after one month. And the 12-month event-free survival and overall survival rates were 50% and 76%. More mature survival data from ELIANA shows a two-year relapse-free survival rate of 61% among those achieving remission. Like Sue and Damian, the patients in this trial were heavily pretreated with a median of three prior regimens and 61% had previously undergone transplant. Knowing that many patients can survive long term with no further therapy post-CAR T cell infusion, there is limited enthusiasm for a second transplant among physicians, patients, or their parents if a good response is obtained and maintained. So for Sue, I would recommend close monitoring, but no additional therapy as long as she showed continued evidence of response for 6 to 12 months. I would repeat bone marrow MRD testing at 60 and 90 days and every three months thereafter, and measure peripheral blood B cell numbers monthly for at least six months. B cell depletion is a good surrogate for CAR T cell activity, as normal CD19 positive cells are also killed. If Sue remains MRD negative and has no circulating CD19 positive B cells for at least six months, then there is a good hope that no more therapy is needed. Damian is a more complicated case, as he has never undergone transplant and has an HLA-identical donor, and now has excellent disease control and is in good medical condition to undergo a transplant. There are short-term risks of transplant with a 100-day mortality risk of 5% to 10% for a teenager. And there are also long-term risks related to the transplant procedure and/or graft versus host disease. The long-term risks of tisagenlecleucel appear limited other than the persistent B cell depletion, but the longest followup is only eight years, and few patients have more than five years of followup. So we have no idea about the efficacy and potential risks 10 to 20 or more years post-infusion. Damian failed three induction attempts. If his leukemia comes back, one may never be able to get him back into a healthy MRD negative remission. So there is a good argument that his best chance for definitive therapy is with transplant. Given this, many would strongly recommend transplant as consolidative chemotherapy for Damian. However, it's also possible that Damian has now received curative therapy and will never relapse. Highlighting the uncertainty surrounding this question, our group at CHOP, which has treated over 300 patients with relapsed refractory ALL with CAR T cells, does not have a clear consensus on what to do for patients like Damian. It's our practice to summarize the potential advantages and disadvantages of transplant versus no further therapy, and help the patient and their family decide what is the best course for them. To summarize, tisagenlecleucel is an exciting therapy that provides new opportunities for children and young adults with relapsed and refractory ALL. However, the field of cellular immunotherapy is young, and there are many uncertainties, particularly surrounding the issue of definitive therapy versus bridge to transplant. Today, we lack the followup data needed to make definitive statements, and patients and families need to understand that and be full partners in these complicated decisions. Thank you very much for listening. Thank you for listening to this week's episode of the ASCO eLearning weekly podcast. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive eLearning center at elearning.asco.org.

Dr. Raja Mudad is a medical oncologist specializing in lung cancer at Florida Precision Oncology. In today's ASCO eLearning Podcast, Dr. Mudad will discuss two patient cases related to the treatment of advanced non-small cell lung cancer harboring an EGFR mutation. While the two cases are similar, the recommended treatments can be different. We hope you enjoy this episode. To hear the latest eLearning Podcast episodes as soon as they are available, please subscribe on Apple Podcasts [https://podcasts.apple.com/us/podcast/asco-elearning-weekly-podcasts/id1375021523] or Google Play [https://play.google.com/music/listen?u=0#/ps/Igjyhvqqrvuc5mjvlljhzkpvgeu]. We truly value your feedback, so please leave a review. To access our entire library of podcasts and other amazing eLearning content, visit elearning.asco.org [https://elearning.asco.org/homepage]. The purpose of this podcast is to educate and inform. This is not a substitute for 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. Hello. My name is Raja Mudad. I'm a medical oncologist specializing in lung cancer. I work at Florida Precision Oncology, a practice dedicated to an academic approach in the treatment of cancer. Today, we compare two patient cases that relate to the treatment of advanced stage non-small cell lung cancer harboring an EGFR mutation. These two cases have similarities, yet the recommended treatments may be different. Let us look at the cases. Patient case 1, our first patient case is Roberto. He is a 34-year-old man with stage 4 non-small cell lung cancer harboring an EGFR deletion 19 mutation. The patient, a never smoker, presented with chest pain and was diagnosed with a pulmonary embolus. CT scan of the chest also demonstrated bilateral lung nodules. Biopsy revealed adenocarcinoma. Staging workup revealed multiple small brain metastases. Patient case 2, our second patient case is Heidi. She is a 60-year-old woman with stage four non-small cell lung cancer with an exon 21 mutation in EGFR gene. She presented with a cough. A CT scan of the chest showed a left lung mass. An endobronchial ultrasound guided biopsy revealed no evidence of mediastinal disease. And a biopsy was positive only in the mass showing adenocarcinoma. She was taken to surgery but found to have multiple pericardial nodules. No distant metastases were seen on the PET scan. The two cases are clinically similar. Would any of the differences lead you to select a different treatment for each patient? Let's take a look. The two patients have the exact disease, a similar stage, and mutations in the same EGFR gene. Their initial treatment is the same. The initial treatment in both cases, osimertinib, is considered the standard of care in the United States, with a median progression-free survival of 19 months. Roberto started on treatment with osimertinib, and the follow-up PET scan and brain MRI showed complete resolution of all of the abnormalities. In the second case, surgery was aborted, and the patient started on osimertinib. About 1.5 years after Roberto started on osimertinib, progressive disease developed with a new adrenal mass, a new bone metastasis, and progression in the brain. He received stereotactic radiosurgery to the brain. A repeat biopsy of the adrenal mass revealed the same histology but with a MET amplification detected on next-generation sequencing. About eight months after starting osimertinib, Heidi developed progressive disease, and a repeat biopsy confirmed the same histology and the original EGFR mutation but no additional abnormalities. As you can see, the two cases are similar at presentation. However, upon progression, both cases have peculiarities that make them different. Which differences in the two cases do you think may inform treatment choices? Would the differences lead your choice of treatment in a different direction, or would both patients receive the same treatment? If treatment is different, what is the difference that changes your choice of treatment? The standard of care for non-small cell lung cancer with an EGFR mutation upon progression on first-line tyrosine kinase inhibitor is generally chemotherapy, possibly combined with immunotherapy. In non-small cell lung cancer with an EGFR mutation, there are multiple suggested mechanisms of resistance to osimertinib. These involve new mutations in the EGFR gene, alterations in parallel or downstream oncogenes, such as MET, KRAS, and PIK3CA, or histological transformation to small-cell carcinoma. MET amplification is a very common abnormality seen in those patients. Upon progression, patients have several options, and their treatment should be directed based on the results of the repeat molecular evaluation. That is why it is important to repeat a biopsy on patients with disease progression. Nowadays, liquid biopsy is also helpful in detecting these abnormalities without the need for an actual biopsy. Roberto can benefit from a MET-directed therapy using a tyrosine kinase inhibitor. He did receive stereotactic radiosurgery to the brain due to the presence of mild symptoms. He is clinically doing well, so the need to initiate immediate systemic cytotoxic chemotherapy is not urgent. In this patient, I would offer him an oral MET inhibitor and repeat his imaging in three months. On the other hand, the second patient, Heidi, did not have an actionable mutation upon re-biopsy. The patient is best served by a clinical trial. However, if a trial is not available, or if she is not eligible, then systemic chemotherapy and immunotherapy would be the standard of care. In my practice, and based on the results of the IMpower 150 trial, the use of the combination of carboplatin, paclitaxel, atezolizumab, and bevacizumab is preferred. The subset analysis of the EGFR-positive patients in this trial favored the use of the quadruplet combination. Thank you for listening to this episode of the ASCO eLearning Podcast. For more information on the treatment of non-small cell lung cancer, including additional patient cases and opportunities for self-evaluation, please visit the comprehensive eLearning center at elearning.asco.org. Thank you for listening to this week's episode of the ASCO eLearning weekly podcast. To make this part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive eLearning center at elearning.asco.org.

Dr. Doug Johnson is an Associate Professor of Medicine and Leader of Melanoma Program at the VanDr. Doug Johnson is an Associate Professor of Medicine and Leader of Melanoma Program at the Vanderbilt Ingraham Cancer Center in Nasheville, TN. In today's ASCO eLearning Podcast, Dr. Johnson discusses two patient cases related to stopping of anti-PD-1 and consideration of retreatment for metastatic melanoma. While the two cases are similar, the recommended treatments can be different. We hope you enjoy this episode. To hear the latest eLearning Podcast episodes as soon as they are available, please subscribe on Apple Podcasts [https://podcasts.apple.com/us/podcast/asco-elearning-weekly-podcasts/id1375021523] or Google Play [https://play.google.com/music/listen?u=0#/ps/Igjyhvqqrvuc5mjvlljhzkpvgeu]. We truly value your feedback, so please leave a review. To access our entire library of podcasts and other amazing eLearning content, visit elearning.asco.org [https://elearning.asco.org/]. The purpose of this podcast is to educate and inform. This is not a substitute for 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. Hello, my name is Doug Johnson. I'm an associate professor of medicine and leader of the Melanoma Program at Vanderbilt-Ingram Cancer Center. Today we compare two patient cases that relate to stopping of Anti PD-1 therapy in consideration of whether to re-treat patients that have metastatic melanoma. These two cases have similarities, yet the recommended treatments may be different. Let's look at the cases. Patient case one. Our first patient case is Dave. Dave is a 62-year-old man with metastatic melanoma involving the lungs and liver. He was treated with single agent nivolumab and he had decreasing size of one of his lung metastases but had increasing liver metastases when his first CT scan was performed. Since his melanoma has a BRAF V600e mutation, he was switched to BRAF and MEK inhibitors, which were later followed by progression and 12 months on therapy. Patient case two. Our second patient case is Rachel. Rachel's a 55-year-old woman with metastatic BRAF wild type melanoma involving the lungs and liver as well. She receives pembrolizumab with a complete response and therapy is stopped after 15 months of treatment. Two years later, she has growth of two of her lung lesions and a biopsy confirms that this is melanoma. So questions for consideration. As you can see, both cases involve progression of anti PD-1 therapy, but there are some differences. Do the differences lead your choice of treatment in a different direction, or would both patients receive the same treatment? In particular, would you consider anti PD-1 re-treatment for either or both of these patients? Some background. The standard treatment for metastatic melanoma, regardless of BRAF mutation status, is Anti PD-1 monotherapy, either with nivolumab or pembrolizumab. Approximately 44% of patients experience complete responses to treatment, many of which are durable. Many patients with complete or near complete responses have a discussion with their oncologist and elect to stop treatment after one to two years on therapy. However, about one third of patients who have a response ultimately experience disease progression. The treatments who either respond to Anti PD-1 and then later progress or patients who never respond at all is an important issue to consider. Options for these patients include ipilimumab monotherapy, ipilimumab in combination with nivolumab, or if BRAF mutated, BRAF and MEK inhibitor therapy. Re-treatment with Anti PD-1 may be an option as well. Other melanoma therapies have shown benefit with re-treatment with this type of strategy. For example, patients re-treated with BRAF and MEK inhibitors, provided they took at least a six week break off therapy, have nearly a 50% response rate to re-treatment. In addition, patients who benefited from ipilimumab then later progressed had at least a 20% response rate to re-treatment. So how are these cases related? Both patients experienced progression either on or following Anti PD-1 treatment. However, there are some key differences as well. Patient one progressed while still receiving treatment, and at least his liver lesions never responded to therapy at all. On the other hand, patient two experienced progression a long interval after completing treatment. She also had an objective response, in fact, a complete response to her initial course of therapy. So what should we do with these patients? Well, the answer, from my perspective, is patient one should not receive re-treatment with Anti PD-1 therapy. A recent publication by Dr. [? Betof ?] and colleagues in JCO studied 396 patients with long-term follow-up following Anti PD-1 treatment. This included 34 patients who were re-treated. None of the patients who initially progressed on therapy, so those who didn't have a complete response, were prolonged stable disease. None of those patients experienced long-term benefit with re-treatment. On the other hand, these patients did benefit from ipilimumab and nivolumab 25% of the time, with a 25% response rate. Additional patients also experienced stable disease in this group. Thus, either ipilimumab and nivolumab or [INAUDIBLE] monotherapy should be considered for patient one. Patient two, by contrast, had a durable complete response to therapy and progressed after completion of treatment. This patient could consider re-treatment with Anti PD-1. A study by Dr. Warner suggested that of patients in this position, those who had an initial objective response to treatment, only 15% of patients had objective responses. However, durable benefit was more frequently seen in patients who had complete or partial response to their initial course. Many patients had prolonged stable disease with re-treatment. Thus, re-treatment could be considered in this patient. Or we would also be reasonable to think about ipilimumab and nivolumab combination or ipilimumab alone. That would also be appropriate for this patient. In closing, thank you for listening to this week's episode of ASCO e-learning weekly podcast. For more information on treatment for metastatic melanoma, including additional patient cases and opportunities for self-evaluation, visit the comprehensive e-learning center at e-learning.asco.org. Thank you. [MUSIC PLAYING] Thank you for listening to this week's episode of the ASCO e-learning weekly podcast. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at e-learning.asco.org.

Dr. Rodrigo Munhoz is a Melanoma/Sarcoma Oncologist at Hospital Sírio Libanês in São Paulo, Brazil. In today's ASCO eLearning Podcast, Dr. Munhoz discusses two patient cases related to challenges and barriers to treating cancer in developing countries. While the two cases are similar, the recommended treatments can vary depending on social, economic, cultural, religious, patient knowledge and other aspects. We hope you enjoy this episode. To hear the latest eLearning Podcast episodes as soon as they are available, please subscribe on Apple Podcasts or Google Play. We truly value your feedback, so please leave a review. To access our entire library of podcasts and other amazing eLearning content, visit elearning.asco.org The purpose of this podcast is to educate and inform. This is not a substitute for 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. Hello, my name is Rodrigo Munhoz, and I'm a melanoma and sarcoma medical oncologist at Hospital Sirio Libanes in Brazil. Today, we compared two patient cases treated in Brazil that describe challenges related to the access to systemic therapies for advanced melanoma in developing countries. These few cases share similarities. Yet, the recommended treatments can be largely different based upon sociocultural and religious aspects, among other variables that influence patients' choices, including enrollment into clinical trials. Let's look at the cases. Our first patient is Paolo, a 49-year-old man diagnosed with metastatic melanoma with asymptomatic CNS involvement in addition to lung and subcutaneous metastases. The patient was diagnosed with an intermediate risk primary melanoma of the right arm without nodal involvement a couple of years before. He presented for treatment considerations following disease relapse in the form of M1d disease with normal serum LDH level. Decision was made to proceed with first-line treatment with a combination of ipilimumab and nivolumab, a treatment covered by his private insurance plan. And he's scheduled to receive the first dose. Our second patient case is Rachel, a 65-year-old woman diagnosed with metastatic melanoma harboring a BRAF mutation. Following initial surgical treatment for a high-risk primary melanoma with nodal involvement, she developed short-interval metastasis with CNS, liver, and lung lesions. Although immune checkpoint blockers and BRAF and MAC inhibitors were not provided through the public health system, a clinical trial with a triplet combination of a BRAF inhibitor, MAC inhibitor, and an anti-PD-L1 agent was offered. Following discussions about the clinical trial implications, potential adverse events, and additional aspects described in an informed consent form, the patient declined any additional form of therapy and decided to pursue alternative treatments and healing through religion. As you can see, both cases are very similar in presentation, but with considerable differences in terms of treatment options and decisions. How can differences in access limit the treatment decision-making process and affect the patient's prognosis? How can socioeconomic and religious barriers determine one's decision about enrollment into a clinical trial? Advances in systemic treatment options for melanoma, both in the form of target therapy and immunotherapy through immune checkpoint blockade, have deeply altered the scenario for patients affected by this challenging disease. As an example, in a recent randomized trial, 52% of the patients with advanced melanoma treated with a combination of nivolumab and ipilimumab and 44% of those receiving single-lesion nivolumab were alive at five years. Similarly, a pooled analysis of patients receiving dabrafenib and trametinib showed robust activity of BRAF and MAC inhibitors in metastatic disease with response rates approaching 70% and almost 35% of the patients alive at five years. The efficacy of these agents was also demonstrated in patients with CNS metastases. These advances were also noted in the adjuvant setting. In randomized trials that included a majority of patients with stage III disease, pembrolizumab, nivolumab, or dabrafenib and trametinib resulted in significant gains in recurrence-free survival. Yet, these major breakthroughs are not homogeneously available throughout the globe. And many countries still face restricted access and significant inequalities in the treatments made available to the population. As an example, in Brazil, systemic treatment options offered through the public health system, which covers 80% of the population, are still largely limited to cytotoxic chemotherapy with DTIC being the most frequently prescribed agent. In this setting, enrollment into clinical trials represents an effective way to partially overcome these hurdles, extend the offer of active agents, and reduce these gaps. However, the conduction of a clinical trial brings additional challenges. In the cases described here, although very similar in presentation, several aspects were determinant in both medical and patient decisions, which may lead to distinct outcomes. For patient one, a standard-of-care treatment in line with the best scientific evidence was offered and available. In the second case, optimal care was limited by access issues. In addition, despite the possibility of inclusion in a promising clinical trial, social and religious aspects were also determinant in the patient decision. Despite the advances in screening, diagnosis, and treatment of solid tumors, including melanoma, access inequalities pose major challenges and demand a global agenda. Clinical research is an effective tool in reducing gaps and disparities in developing countries, but also largely influenced by cultural, social, and religious aspects, as exemplified by the cases described in this podcast. Initiatives designed to optimize access in developing countries must encompass not only a framework adapted to provide value-based care, but also effective education and communication tailored to patient preferences, as an example, religious belief, and socioeconomic status in discussions of treatment decisions. Thank you for listening to this week's episode of the ASCO eLearning weekly podcast. For more information on the treatment of melanoma in global oncology, including additional patient cases and opportunities for self-evaluation, visit the comprehensive eLearning center at elearning.asco.org. Thank you for listening to this week's episode of the ASCO eLearning weekly podcast. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive eLearning center at elearning.asco.org.

In this month's ASCO eLearning Podcast, Dr. Helen Chew, Professor of Medicine and leader of the Clinical Breast Cancer Program at University of California Davis Comprehensive Cancer Center, brings us two patient cases on systemic therapy for metastatic triple negative breast cancer. This podcast episode appears as a resource in ASCO eLearning's recently updated Genetics & Genomics course collection in the course Hereditary Breast and Ovarian Cancer Syndrome. Click the links to learn more about these courses, including CME and MOC credit details. If you are interested in purchasing a course or the entire collection, go to shop.asco.org Transcript Hello, my name is Helen Chew. I am Professor of Medicine and leader of the Clinical Breast Cancer Program at the University of California Davis Comprehensive Cancer Center. Today, we compare two patient cases on systemic therapy for metastatic triple negative breast cancer. Systemic therapy for metastatic triple negative breast cancer remains a challenge. The mainstay of therapy is cytotoxic chemotherapy. In March 2019, based on the Impassion130 trial, the anti-PD-L1 antibody, atezolizumab, was approved in combination with nab-paclitaxel for metastatic triple negative breast cancer that expresses PD-L1. However, for triple negative breast cancer without PD-L1 expression, immunotherapy is not an option. In addition, there are many indications for genetic counseling and testing, including patients diagnosed with breast cancer at age 45 years or younger and patients with triple negative breast cancer diagnosed at age 60 years or younger. Results of genetic testing may influence treatment options in metastatic breast cancer. Before we explore treatment options, let's look at two similar cases where treatment choices may differ. Can you identify the key differences? Let's begin with Case 1, a 45-year-old woman with metastatic triple negative breast cancer to the liver and lungs. Two years earlier, she had received preoperative anthracycline and paclitaxel for a stage II, triple negative breast cancer. She had a limited family history of cancer and underwent genetic counseling and testing. No pathogenic mutations were found in a panel of genes associated with hereditary cancers. At the time of her metastatic recurrence, biopsy of a liver lesion confirmed metastatic carcinoma, consistent with triple negative breast cancer. There was no PD-L1 staining. The patient received carboplatin and gemcitabine for 6 cycles. She now has disease progression. Case 2 is a 57-year-old woman who also has metastatic triple negative breast cancer involving the chest wall, liver and bones. Three years earlier, she had received adjuvant anthracycline and paclitaxel for a stage II, triple negative breast cancer. She had no family history of breast or ovarian cancer, but underwent genetic counseling and testing revealing a pathogenic germline BRCA1 mutation. At the time of metastatic recurrence, chest wall biopsy confirmed metastatic triple negative breast cancer with no PD-L1 staining. The patient received carboplatin for 6 cycles with an initial response. Nine months later, she has disease progression. In each of these cases, what option would you recommend for subsequent therapy? The choices include additional chemotherapy, such as capecitabine, eribulin or vinorelbine, or a PARP inhibitor. In Case 1, the correct answer is chemotherapy, including any of the named options. This patient does not harbor a germline BRCA mutation so would not benefit from a PARP inhibitor. In Case 2, the correct answer is a PARP inhibitor. In both the OlympiAD and EMBRACA phase III trials, patients with germline BRCA mutations and previously treated HER2-negative metastatic breast cancer were randomized to either chemotherapy of physicians' choice or to olaparib or talozoparib, respectively. Approximately 40-50% had triple negative metastatic breast cancer in these two trials. Patients who received the PARP inhibitors had significantly improved progression-free survival compared to chemotherapy in both trials. Both PARP inhibitors, olaparib and talozoparib, are approved for patients with HER2-negative metastatic breast cancer who have germline BRCA mutations. These two cases of metastatic triple negative breast cancer share similarities. Both cases met criteria for genetic counseling and testing, including the young age at diagnosis for Case 1 and the diagnosis of triple negative breast cancer at age 60 or younger in Case 2. Both cases were treated similarly at initial presentation and on metastatic recurrence. However, the key difference is that no pathogenic mutation was detected in Case 1. In contrast, a germline BRCA1 mutation was found in Case 2. PARP inhibitors are associated with improved progression-free survival compared to the chemotherapy given in the OlympiAD and EMBRACA trials in patients with germline BRCA mutations and HER2 negative, previously treated metastatic breast cancer. In addition, although both cases received a platinum-based regimen at metastatic recurrence, the TNT trial revealed that only patients with germline BRCA mutations and triple negative metastatic breast cancer had improved progression-free survival with carboplatin compared to docetaxel. No difference in progression-free survival was seen in the trial population of triple negative metastatic breast cancer without a germline mutation. Thank you for listening to this week's episode of the ASCO eLearning Weekly Podcast. For more information on the treatment of metastatic breast cancer, including additional patient cases and opportunities for self-evaluation, visit the comprehensive eLearning center at elearning.asco.org

Dr. Winston Tan, Medical Oncologist at Mayo Clinic, discusses the recent FDA approval of erdafitinib and enfortumab for second-line treatment of metastatic bladder cancer.

An interview with Dr. Scott Eggener of University of Chicago Medicine on "Molecular Biomarkers in Localized Prostate Cancer: ASCO Guideline." This guideline provides recommendations for available tissue-based prostate cancer biomarkers geared toward patient selection for active surveillance, identification of clinically significant disease, choice of postprostatectomy adjuvant versus salvage radiotherapy, and to address emerging questions such as the relative value of tissue biomarkers compared with MRI. Read the full guideline at www.asco.org/genitourinary-cancer-guidelines

An interview with Dr. Melissa Dillmon on the Patient-Centered Standards for Medically Integrated Dispensing: ASCO/NCODA Standards. The interview covers the findings of the systematic review, which were consistent with the NCODA patient-centered standards for patient relationships and education, adherence, safety, collection of data, documentation and other areas. NCODA standards were adopted and used as basis for these ASCO/NCODA standards. Additional information is available at www.asco.org/mid-standards.

An interview with Dr. Naren Ramakrishna from University of Florida Health Cancer Center at Orlando Health on the guideline update which addresses management of brain metastases for patients with human epidermal growth factor receptor 2–positive advanced breast cancer. Read the full guideline at www.asco.org/breast-cancer-guidelines