Podcasts about charu aggarwal

Dr. Vamsi Velcheti and Dr. Charu Aggarwal discuss the evolution of ctDNA as a critical tool in precision oncology and its implications for lung cancer management, including its potential role in the early-stage setting. TRANSCRIPT Dr. Vamsi Velcheti: Hello. I am Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast today. I am a professor of medicine and director of thoracic medical oncology at the Perlmutter Cancer Center at NYU Langone Health.  The management of small cell lung cancer has rapidly evolved over the past few decades, and today, molecular testing and biomarker testing for lung cancer are absolutely critical in terms of designing treatment options for our patients with metastatic non-small cell lung cancer. Today, I'm delighted to be joined by Dr. Charu Aggarwal for a discussion on ctDNA (circulating tumor DNA) and the role of ctDNA in lung cancer management. Dr. Aggarwal is the Leslye Heisler Professor of Lung Cancer Excellence and section chief of thoracic and head and neck oncology at University of Pennsylvania Abramson Cancer Center.  You'll find our full disclosures in the transcript of that episode.  Dr. Agrawal, it's great to have you on the podcast today. Thank you for being here. Dr. Charu Aggarwal: Thank you for having me. Dr. Vamsi Velcheti: Let's start off with setting the stage for ctDNA technology. These technologies have rapidly evolved from experimental conceptual stage to essential clinical tools for day-to-day clinical practice. Could you briefly discuss how recent advancements in ctDNA technologies are shaping our approach to precision medicine, especially in lung cancer? Dr. Charu Aggarwal: Absolutely. And you know, I think we need to just level set a little bit. What exactly is circulating tumor DNA? This is a way to assess exactly that. Every tumor sheds little pieces of tumor-derived DNA into the bloodstream, and this occurs in a variety of solid tumors. But now we have the technology to be able to derive this DNA that's actually being shed from the tumor into the bloodstream, these minute fragments of DNA, take them out, amplify them and sequence them with a variety of different mechanisms. They can be DNA sequencing alone, they can be DNA and RNA sequencing, they can be whole transcriptome sequencing. The technology, as you rightly pointed out, Dr. Velcheti, has significantly improved from just being able to look at circulating tumor DNA to now being able to amplify it, sequence it, and use it to offer personalized therapy. I think lung cancer is definitely the poster child for such an approach as we have a lot of data that has shown clinical utility and validity of being able to use circulating tumor DNA next-generation gene sequencing to guide therapy. Dr. Vamsi Velcheti: There have been so many technological leaps. It's really impressive how far we've come to advance these sequencing platforms. Recent advances with AI and machine learning are also playing important roles in interpreting ctDNA data. How are these computational advances really enhancing clinical decision-making in day-to-day clinical practice? Dr. Charu Aggarwal: I think while we have firmly established the role of ctDNA in the management of patients with metastatic lung cancer, some of the approaches that you talked about are still experimental. So let me backtrack a little bit and set the stage for how we use ctDNA in clinical practice right now. I think most patients, when they come in with a new diagnosis of stage IV lung cancer, we want to test for biomarkers. And this should actually be the established standard. Now included in the NCCN guidelines and actually also international guidelines, is to consider using blood-based testing or plasma-based testing to look for biomarkers, not just tissue-based testing which had been our historical standard, but to use these plasma guided approaches to identify the seven to nine biomarkers that may be truly implicated in either first- or second-line therapy that are called as your immediately actionable mutations.  What you're talking about is AI computational methods. I think there's a lot of excitement about how we can use genomic signatures that are derived from either tissue or ctDNA-based biomarker testing, combine it with radiomic features, combine it with histologic features, look at H & E patterns, use AI algorithmic learning to be able to actually predict recurrence scores, or can we actually come up with predictive signatures that may be extremely helpful?  So, I think some of the techniques and technologies that you're talking about are incoming. They are provocative. I think they're very exciting, but very early. Dr. Vamsi Velcheti: I think it's really amazing how many advances we have with these platforms. You know, the challenge really is the significant gap in terms of uptake of molecular testing. Even today, in 2025, there are significant gaps in terms of all metastatic lung cancer patients being tested for all biomarkers.  So, why do you think there's such a challenge in testing patients with lung cancer? In most academic practices, we try to achieve 100% testing for all our patients, but we know from recent studies that that's not the case across the country. What do you think the gaps are? Dr. Charu Aggarwal: Biomarker testing is so essential, like you pointed out, for us to be able to guide the right therapy for our patients. And we see this in our practice every day as you and I see patients with lung cancer, that a large proportion of our patients either don't get tested or they start therapy before their test results come back. So, I think this is a real problem.  However, to add some optimism to this problem, I do think that we are making a move in the right direction. So, four or five years ago, there was a lot of data being presented at national meetings, including ones from the American Society of Clinical Oncology, where we saw that, nationally, the rates of biomarker testing were probably in the rate of 40 to 50%. However, now with the availability of both tissue and plasma, I do think that the rates of biomarker testing are increasing. And if you were to survey a sample or even perform retrospective data research, I believe that the number is closer to 70% of all patients with metastatic non-small cell lung cancer.  And you know, you asked why is it not 100%? I think there are many reasons. I think the number one reason is tissue availability. Many times, the biopsies are small, or the tumor is very necrotic. So, either the tissue quantity itself is small, or the tissue quantity is insufficient to perform gene sequencing. And that's exactly where plasma comes in. When you don't have tissue availability, we have shown, as have others, that you can use plasma effectively to increase the proportion of patients who are not only tested but also receive the right therapy. I think there are also other barriers, including inertia. You know, I think this is both patient and physician inertia, where patients want to get started quickly, they don't want to wait. Physicians are very busy and sometimes want to be able to deliver treatment as soon as possible. We have seen there are some institutional barriers. Not every institution has in-house gene sequencing testing. So how do you really operationalize, send out these tests in a fast, efficient manner so that you get results back? Is it a pathologist who sends out the test? Is it the medical oncologist? Is it the pulmonologist or the interventionalist? I think there is this need to develop reflex testing mechanisms which some institutions do really well and some don't. And then finally, there are financial implications as well. How do we do this in a most cost-efficient fashion?  So there are many barriers, but I'm happy to say that we are making a move in the right direction as we are understanding that it's important to do it, it's easy to do it maybe with a value add of plasma, and finally, as you said, you know, as these technologies become more available, they're actually getting more cost-effective. Dr. Vamsi Velcheti: Dr. Aggarwal, you've been at the cutting edge of these advanced platforms and testing. So, what do you do in UPenn? How do you handle all these barriers and what is your workflow for patients in University of Pennsylvania? Dr. Charu Aggarwal: One of the things that I mentioned to you was there may be institutional barriers when it comes to gene sequencing. So, we actually, several years ago now, instituted a very robust reflex testing paradigm where almost all of our patients, regardless of stage, with a non-squamous non-small cell lung cancer diagnosis, would automatically be reflexively sent to our molecular pathology lab where they would get gene sequencing both for the DNA as well as with an RNA fusion-based platform. And the reason we did this was because we wanted to expedite and reduce the turnaround time. We also wanted to ensure that we were not just doing DNA testing, which I think is really important for our listeners here. There are many fusions as well as certain skipping mutations like MET exon 14 that may be missed on DNA testing alone. So, it's really incredibly important to run both DNA and RNA samples.  So, we do this routinely, and based on our research and others, what we also do routinely is that we send concurrent tissue and liquid biopsies or plasma MGS testing upon initial diagnosis. For example, if a patient comes in with a diagnosis of stage IV non-small cell lung cancer, their tissue might already be at my molecular pathology lab based on the reflex mechanism that I just described to you. But upon their initial meeting with me, we will send off plasma. And I will tell you this, that Penn is not just one institution, right? We have a large network of sites. And as part of my research, one of the things that we wanted to do was implement wide scale means to improve biomarker testing. And we have done this with the use of technology like you mentioned, Dr. Velcheti: How can we actually use AI? How can we leverage our electronic medical record to identify these patients? So, we have a nudge-based mechanism which actually facilitates the pending of orders for biomarker testing for patients with new diagnosis of metastatic non-small cell lung cancer. And we are looking at our rates of biomarker testing but also rates of completion of biomarker testing before first-line therapy started. So many of our participating sites are clusters for our randomized control trial to increase molecular testing. And I'm really excited about the fact that we're able to implement it not just at our main satellite, downtown Penn Hospital, but also across our community. Dr. Vamsi Velcheti: I think that's great. Thank you so much for those insights, Dr. Aggarwal. I think it's so important because having the best technology is just not enough. I think implementation science is actually a real thing. And I think we need to all learn from each other, advance these things.  So, I want to ask you about the new emerging paradigm in terms of using ctDNA. Of course, in the metastatic setting, we've been using ctDNA for molecular profiling for a while now. But the recent data around monitoring early-stage disease, especially post-operative monitoring, is an exciting area. There are a lot of opportunities there. Could you please talk us through the emerging data in lung cancer and how do we incorporate ctDNA-based monitoring MRD or should we even do that right now? Is the data ripe enough for us to kind of deploy this in a clinical setting? Dr. Charu Aggarwal: I think using ctDNA in the early-stage setting is our next frontier in lung cancer. I think naturally we have been able to successfully deploy this in the stage 4 setting. It made a meaningful difference in the lives of our patients, and we are a little bit behind the A ball in terms of how MRD is used in lung cancer. Because, you know, colorectal cancer has already done large-randomized trials based on ctDNA and MRD. It's routinely used in hematological malignancy. So, it makes sense that we should start to use it.  However, when I say this, I say this with excitement, but also a little bit of gentle caution saying that we actually don't quite have the prospective randomized data just yet on how to deploy. Yes, intuitively we would say that if you detect ctDNA and MRD, that patient is at higher risk. So, we identify that, but we actually don't know what to do with the second part of that information once you identify a patient with high risk. Are there other techniques that we can then come in with or other drugs that we can come in with to modify that risk? And that's the thing that I think we don't have right now. The other thing that we don't have right now is the timing of the assay, when to use it. Is it to be tested in the pre-op setting? Is the post-op test the best timing, or is it monitoring and dynamics of ctDNA that are most important? And the third thing I will say in terms of precautionary cause is that we don't know which test just yet. There are actually a few commercially available tests out in the market right now. We know about them and I'm sure our community colleagues know about them. Some of them even have Medicare approval. However, many of these tests are currently tissue informed. We don't have tissue uninformed tests. And what does that mean? Tissue uninformed means that you actually take a piece of tumor tissue, you sequence that tumor and based on the gene profile of that tumor, you actually design a panel that can then be used to track the mutations in the blood-based pack. This requires, as the name implies, a tumor. So can this be used in the pre-op setting is a large question. Because coming back to the idea of tissue availability, you and I both know that when we get FNAS and we use it for PDL-1 testing and we use it for gene sequencing, there often isn't enough tissue left for us to then either do whole genome sequencing or even whole transcriptome sequencing, which may be required to build some of these assays.  I think the future lies in this idea of tumor uninformed assays because if we could go to a blood only or a plasma only approach using novel signatures like proteomics or methylation, I think that's where the future is. But we're still a little bit early in the discovery stages of those, as well as to come are the validation stages so that we can be confident that these blood-only assays may actually give us an answer.  So, with those three cautionary notes, I would say that optimism is still very high. I think ctDNA MRD is the right place to think about. We need to do this for our patients to better identify high-risk patients and to think about means to escalate treatment for them. Dr. Vamsi Velcheti: Yeah, I completely agree, and I think with all the changes and evolution of treatments in the management of early-stage lung cancer now with neoadjuvant and adjuvant, there's really a need for an escalation and de-escalation of therapies post-operatively. And I think it's a huge opportunity. I think we all could learn from our colorectal colleagues. I think they've done a really good job at actually doing prospective trials in this setting. I think we're kind of a little behind here.  Dr. Charu Aggarwal: I think in the metastatic setting there are ongoing trials to look at this exact question. How do you choose an appropriate first-line therapy, a monitor ctDNA at the six-week trial? It's being evaluated in a trial called the “Shedders” trial, where if patients are still ctDNA positive at six weeks, then you can escalate treatment because they haven't “cleared” their ctDNA. There has been a lot of research that has shown that lack of ctDNA clearance in the metastatic setting may be a poor prognostic factor. We and others have shown that if you do clear your ctDNA or if you have a reduction in ctDNA load overall, that that is directly related to both an improved progression-free survival and overall survival. This has been shown with both tissue informed and uninformed assays. So I think it's very clear that yes, you can track it. I think the question is: Can you apply that data to the early-stage setting? And that's an open research question. A lot of groups are looking at that and I think it's completely reasonable, especially to determine duration of therapy, to determine optimal timing, optimal timing of scans even. And I think these are just such interesting questions that will be answered in the future. Dr. Vamsi Velcheti: And also like a kind of early detection of resistance patterns that might inform early initiation of combination strategies. And I think it's a lot of opportunities I think yet to be explored. A lot of exciting things to come and I'm sure we'll kind of see more and more data in the next few years.  Dr. Aggarwal, thank you so much for sharing your fantastic insights today on the ASCO Daily News Podcast. It's been a pleasure to have you on the podcast today. Hope to see you at ASCO. Dr. Charu Aggarwal: Thank you so much. This was great and I remain so excited by all of the possibilities to improve outcomes for our patients. Dr. Vamsi Velcheti: Thank you to all the listeners for your time today. If you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcast. Thank you so much. Disclaimer: 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. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement. Follow today's speakers:  Dr. Vamsidhar Velcheti  @VamsiVelcheti  @vamsivelcheti.bsky.social Dr. Charu Aggarwal @CharuAggarwalMD   Follow ASCO on social media:  @ASCO on X (formerly Twitter)  ASCO on Bluesky ASCO on Facebook  ASCO on LinkedIn    Disclosures: Dr. Vamsidhar Velcheti:  Honoraria: Glavanize Therapeutics Consulting or Advisory Role: Bristol-Myers Squibb, Merck, AstraZeneca/MedImmune, GSK, Amgen, Taiho Oncology, Novocure, Takeda, Janssen Oncology, Picture Health, Regeneron Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline  Dr. Charu Aggarwal: Consulting or Advisory Role: AstraZeneca, Daiichi Sankyo/AstraZeneca, Regeneron/Sanofi, Pfizer, Boehringer Ingelheim, Takeda, Arcus Biosciences, Gilead Sciences, Novocure, Abbvie Speakers' Bureau: AstraZeneca (an immediate family member) Research Funding (Inst): Merck Sharp & Dohme, AstraZeneca/MedImmune, Daiichi Sankyo/AstraZeneca, Lilly@Loxo, Candel Therapeutics  

In this episode of Meeting Mic, we bring you pearls and perspectives from the 2024 ASCO Annual Meeting, as well as Healio's top headlines from the meeting. Joseph A. Greer, PhD, discusses how early palliative care via telehealth had an equivalent impact on quality of life as in-person visits for patients with advanced non-small cell lung cancer. :27 Charu Aggarwal, MD, MPH, FASCO, further discusses these findings during a press briefing. 3:30 Heinz-Josef Lenz, MD, shares his thoughts on the first-line immunotherapy combination of nivolumab and ipilimumab in colorectal cancer. 4:35 Fumiko Chino, MD, discusses findings on the need for a more effective and transparent prior authorization process to ensure patients receive timely access to essential pain management. 7:09 Suneel Kamath, MD, provides an overview of findings assessing how the microbiome profile of early-onset pancreatic adenocarcinoma is distinct from that of average-onset disease. 10:22 Julie R. Gralow, MD, FACP, FASCO, discusses the important implications of a prospective study on young breast cancer survivors who attempted pregnancy and became pregnant. 12:54      Read the full coverage here: https://www.healio.com/news/hematology-oncology/20240602/we-have-the-technology-telehealth-increases-access-to-palliative-care-for-cancer https://www.healio.com/news/hematology-oncology/20240602/practicechanging-data-support-firstline-immunotherapy-combination-in-colorectal-cancer https://www.healio.com/news/hematology-oncology/20240531/findings-highlight-need-to-improve-prior-authorization-process-for-cancer-pain-management https://www.healio.com/news/hematology-oncology/20240603/tumor-microbiome-profiles-in-pancreatic-cancer-differ-by-age-of-onset https://www.healio.com/news/hematology-oncology/20220611/intramuscular-recombinant-erwinia-asparaginase-active-safe-in-leukemia-lymphoma-subsets Glucose-lowering drugs reduce risk for obesity-related cancers Source: Lin CH, et al. Abstract 10508. Presented at: ASCO Annual Meeting; May 30 – June 4, 2024; Chicago. Chemotherapy regimen improves survival in advanced esophageal cancer Source: Hoeppner J, et al. Abstract LBA1. Presented at: ASCO Annual Meeting; May 31-June 4, 2024: Chicago. Disclosures: Chino reports no relevant financial disclosures. Greer reports a consulting role with BeiGene; research funding from Blue Note Therapeutics and NCCN/AstraZeneca; and royalties from Oxford University Press and Springer Publishing Company. Please see the abstract for all other researchers' relevant financial disclosures.[JJ1]  Kamath reports no relevant financial disclosures.  Lenz reports honoraria from, consulting/advisory roles with, or travel, accommodations or expenses from 3T Biosciences, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Fulgent Genetics, G1 Therapeutics, GSK, Isofol Medical, Jazz Pharmaceuticals, Merck Serono, Oncocyte and Roche. Please see the abstract for all other researchers' relevant financial disclosures.

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. In this podcast, Cancer.Net Associate Editor for Lung Cancer, Dr. Charu Aggarwal, and Cancer.Net Specialty Editor for Thymoma, Dr. Ryan Gentzler, discuss what people with early-stage non-small cell lung cancer should know about their treatment options before and after surgery, called neoadjuvant therapy and adjuvant therapy, respectively. Dr. Aggarwal is the Leslye Heisler Associate Professor of Medicine in the Hematology-Oncology Division at the University of Pennsylvania's Perelman School of Medicine. Dr. Gentzler is a thoracic medical oncologist and Associate Professor of Medicine in the Division of Hematology/Oncology at the University of Virginia (UVA) Comprehensive Cancer Center. View disclosures for Dr. Aggarwal and Dr. Gentzler at Cancer.Net.  To begin, Dr. Gentzler will discuss what people with early-stage non-small cell lung cancer should know about neoadjuvant treatment options before lung surgery. Welcome, Dr. Gentzler. Dr. Gentzler: Hi, this is Ryan Gentzler from the University of Virginia. We're here to discuss the role of neoadjuvant chemotherapy and immunotherapy for the treatment of locally advanced non-small cell lung cancer. So first, I thought I'd address some of the data and definition of what is neoadjuvant treatment. So when we think about treating lung cancer that is not metastatic, that is earlier stage disease, there typically involves multimodality treatment. Sometimes these lesions or tumors can be very small and can be stage I and treated with surgery alone or perhaps radiation alone and no further treatment is needed. But the vast majority of lung cancers that are considered early stage are in fact either larger tumors, involve lymph nodes, and typically fall into the category of stage II or III lung cancers. And these are cancers that often require multiple treatments beyond the local surgery approach alone. When we think about how we deliver that treatment, it can either be given before surgery or after a surgery. If we give treatment before a surgery, we call that neoadjuvant. If it is given after the surgery, we call that adjuvant. And most of the data that we have today in lung cancer uses one or the other of these approaches, and we don't typically give treatments both before and after, at least in terms of the chemotherapy part of that treatment. Historically, most of the data exists in the adjuvant treatment of lung cancer going back several decades that showed that the benefit of chemotherapy after a surgery, particularly for those with stage II and stage III lung cancer, derived a clear benefit of survival by giving chemotherapy after surgery. More recently, with the advent of immune therapy, which we have used in patients with stage IV lung cancer as well as those with stage III lung cancer who cannot undergo surgery, those immunotherapy drugs have been shown to improve overall survival and improve clinical outcomes for a wide range of patients with more advanced disease. And so in the last 4 or 5 years, we have really looked at new trials that have added immunotherapy in what we call perioperative space, either before surgery or after surgery for those that have surgically resectable disease. I'm going to focus on the neoadjuvant approaches that we have seen today, and this largely all started with data from Patrick Forde out of Johns Hopkins and Jamie Chaft from Memorial Sloan Kettering looking at single agent treatment with nivolumab immunotherapy. This was no chemotherapy given for 3 treatments prior to or three cycles prior to surgery. And that trial demonstrated a high degree of patients with tumor reduction and more importantly, we saw that the pathologic response, meaning how much tumor was left under the microscope at the time of surgery, was higher than what anyone anticipated with just immunotherapy alone. That launched a whole series of larger randomized prospective trials evaluating largely the combination of chemotherapy and immune therapy prior to surgery. Now, before we get into some of the results of these trials, I really wanted to emphasize some of the theoretical advantages to neoadjuvant approach. Now, the first potential advantage of giving neoadjuvant treatment is that we know when you start with immunotherapy and chemotherapy regimens and that's the first type of treatment, everyone is guaranteed to get that treatment. And we know that the completion rate prior to surgery is higher than it is after surgery. These patients can get all of the prescribed treatment and will be more likely to get it than if they get it after surgery. So this is one advantage. The other is potentially starting these medications which go throughout the body and treat the cancer, wherever it may be, earlier. We know that one of the risks of all cancers, but lung cancer in particular, is that even with good surgery and removing all of that cancer, there is a chance that there are cancer cells left behind, which leads to risk of recurrence in the years to come after surgery. Naturally, if we start the treatment that can eliminate those cancer cells, wherever they may be, and do that first, perhaps we catch this earlier with fewer cells that have escaped and have a more likely chance of success of eliminating the cancer and resulting in a cure. The third, I think, is one that we still have yet to learn more about, but if we give immunotherapy in particular, these are medications that activate the immune system, particularly the type of immune system cell called a T cell. If that T cell is able to recognize tumor cells, it is more likely to be able to continue to attack those tumor cells. And if we give that treatment prior to removal of the tumor, perhaps that activates the immune system in a more robust way that it can go after these cancer cells and eliminate those that are left behind after the surgery. If you give the immunotherapy after a surgery and the bulk of the tumor, most of the cancer cells have been removed, it may be harder to find those antigens or foreign proteins that are expressed in cancer cells. So the immune system may not be as robustly able to go after cancer if you give it solely after a surgery. Another potential advantage of neoadjuvant approaches is that it really helps us learn as oncologists how well a cancer is responding to a treatment. If we give these treatments for 4 cycles after a surgery, we don't know whether it's eliminating those residual cancer cells or whether it is totally ineffective. If we give it before a surgery and we see that there is tumor reduction or that there is a complete elimination of the cancer, we know that that treatment was an effective treatment at attacking the cancer cells and eliminating them. We know that the cancer was sensitive to that treatment. We can then better prognosticate how well the patients are going to do after surgery. We know based on the latest data that if you achieve what we call a pathologic complete response with chemotherapy and immunotherapy prior to surgery, meaning there are no cancer cells left when we look at that surgical specimen under the microscope, we know that those patients have a much better likelihood of surviving for longer periods of time than those who have active cancer at the time of surgery after prior treatment. And so neoadjuvant approaches allow us in a 2-month time frame to get a great sense of how well our treatments are working and able to prognosticate outcomes based on how well those cancer cells have been eliminated at the time of surgery. One large phase 3 trial called the CheckMate 816 trial was a randomized phase 3 trial and that enrolled patients with stage IB through IIIA non-small cell lung cancer using the old staging system of the 7th edition. These would all now be categorized as stage II and stage III non-small cell lung cancer patients. And it randomized these patients to 3 cycles of chemotherapy plus nivolumab, which is an immunotherapy drug, and compared that to patients treated with chemotherapy alone for 3 cycles. After these 3 cycles of chemotherapy, which is about a 9-week time frame, patients had surgical resection of their tumors. And then after surgery, patients received no further treatment, although treating physicians were allowed to give additional treatments like chemotherapy or radiation if they thought it would be beneficial for these patients, although it was not mandated by the study. One of the first results we saw from this study was that there was a much higher rate of pathologic complete response of 24% of patients achieving a path CR [pathologic complete response] with the nivolumab plus chemotherapy combination compared to only 2.2% with chemotherapy alone. This was highly statistically significant and demonstrated a clear benefit for those receiving the immunotherapy. The other main endpoint of this study was event-free survival, meaning that the time that the patients were alive and without any significant event like cancer progression or death after the enrollment of the trial. And in this analysis, the median event-free survival was significantly longer in those who have received the immunotherapy plus chemotherapy combination prior to surgery. One of the potential concerns about neoadjuvant treatment is that it may render patients unfit for surgery who otherwise could have had their cancer removed. When we look at the outcomes from this CheckMate 816 trial, it actually did not appear to be the case to a large degree. In fact, those that got the nivolumab plus chemotherapy combination were more likely to proceed on with surgery, and the majority did; 83% received the planned surgery. There were patients who were unable to receive surgery due to adverse events of their treatment, but that was only 1% of patients enrolled in the trial. Other reasons for canceling the surgery included disease progression, meaning the cancer got worse to the point where they could not undergo surgery, or other reasons, such as the patient declined surgery, or it was found to be unresectable at the time the surgeon wanted to remove the cancer, or poor lung function.   One of the insights we got from the surgical data from this trial were that those who received the combination of chemotherapy and immunotherapy had slightly higher rates of smaller surgeries like a lobectomy compared to a pneumonectomy for those who had received [chemotherapy alone.] There were also fewer numbers of patients who required a conversion from a minimally invasive surgical procedure to an open surgical procedure if they were getting the immunotherapy combination. A higher number of patients also were able to have complete resection of their tumor if they received the immunotherapy/chemotherapy combination. The length of hospitalization was slightly lower, and the rates of pain were slightly lower in those who received the combination as well. These comparisons were not statistically significantly different, but numerically, there seems to be at least a trend toward benefit in surgical outcomes in this neoadjuvant chemotherapy/immunotherapy approach. And I think this makes sense. We know that this combination is more able to eliminate a cancer and make it a pathologic complete response when we look at it under the microscope, and therefore, if there is shrinking the tumor to a higher degree, naturally, it seems there would be more likely of completely removing the tumor, using a smaller incision to remove that tumor, shortening the length of stay in the hospital and recovery time and pain control. All makes sense if we know that the treatment itself is able to reduce that size of the tumor. There are many other phase 3 trials ongoing studying the impact of immunotherapy plus chemotherapy in the neoadjuvant setting. The AEGEAN trial has recently reported data at the AACR meeting this year in 2023 with similar results that we saw with the CheckMate 816 trial. There are 3 other phase 3 trials that are ongoing, one of which we will see later this summer called the KEYNOTE-671 trial evaluating pembrolizumab plus chemotherapy in the neoadjuvant setting and then 2 other trials evaluating nivolumab, the CheckMate 77T trial, or atezolizumab in the IMpower030 trial. Each of these more recent trials typically have used 4 cycles of chemotherapy plus immunotherapy prior to surgery and also continued the immunotherapy after surgery for a period of time, most commonly approximately 1 year. From the data we have seen so far, it remains uncertain whether additional immunotherapy beyond the 3 or 4 cycles given in the neoadjuvant setting provides any additional benefit. We still do not understand what to do with patients who did not achieve a pathologic response whether further treatment would be of any additional benefit. We do not know if there will be further benefit even in those that achieved a pathologic complete response whether a slightly longer duration of immunotherapy would further improve outcomes in that group. We suspect with longer-term follow-up over the years of all of these phase 3 trials that some of these questions will be answered. So what are some key questions that patients should ask when considering a neoadjuvant chemotherapy/immunotherapy approach? I think the first question that's key is what is my tumor stage? We know that the trials that enrolled patients with a neoadjuvant approach enrolled patients using our current staging system would be a stage II or stage III lung cancer. And this is where it gets really tricky is, what subdivision of stage III is it? We tend to think of stage IIIA's as being one that it would be surgically resectable, with a smaller number of stage IIIBs, and then stage IIIC, one that we would not typically recommend surgery for. I think the next question within the tumor stage is, is this based on imaging or based on the biopsies? And we know that biopsies are really the best way to stage locally advanced cancers, particularly getting samples of lymph nodes in the mediastinum. Sometimes what looks like a stage I or stage II on imaging is, in fact, a stage III based on biopsies that are done at the time of surgery. It's ideal to know that information prior to making the decision about surgery so that that surgery is not futile.   On the opposite side, sometimes there is imaging suggestive of lymph nodes that are enlarged in the mediastinum, and it's presumed that this is a more advanced stage III and is not surgically resectable. However, if you go and biopsy those lymph nodes, sometimes they are benign. Sometimes they are inflammation related to infection or cancer but do not actually contain cancer cells. And so we typically advise that getting biopsies of lymph nodes in the mediastinum, at least any that are particularly suspicious, is highly recommended for these locally advanced cancers. I think the next question that's key to ask is, what are my tumor biomarkers? And there are multiple biomarkers that we look at in non-small cell lung cancer that help us decide what is the best treatment. What is the best approach? What is the best medicine to treat the cancer? We know that one of these biomarkers that is a key is a mutation. So multiple different mutations can occur in lung cancers, particularly those that are adenocarcinoma subtypes. And these mutations may be less likely to benefit from immunotherapy and we may want to take a different approach with surgery, chemotherapy, and potentially targeted therapies that specifically target that mutation that exists in the tumor. The other key biomarker here is PD-L1. We know that tumors with a higher level of PD-L1 are more likely to respond and benefit from immunotherapy. As of right now, that PD-L1 status plays a more important role in the adjuvant setting. All of the chemotherapy plus immunotherapy combinations in the neoadjuvant setting seem to benefit the group as a whole regardless of that PD-L1 status. But still, an important biomarker that we should have prior to making all final decisions on treatment. I think another question that should be asked any time you have an earlier stage cancer is, is my tumor surgically resectable? And there can be many reasons why cancers are not resectable, perhaps due to the anatomy of where the tumor is located, if it invades into the mediastinum, for example, or is near large blood vessels, or perhaps because there are too many lymph nodes and this is a more advanced stage. And so I think the main reasons for not being surgically resectable would be the tumor is too large, if the stage is too high, or is it more of a function of fitness for surgery and that can be because of other underlying lung disease. Perhaps removing part or all of a lung would not be safe due to impaired lung function to begin with. And I think it's important to understand that sometimes stage III lung cancers are resectable and sometimes they are not, and understanding the reason why they are not, I think, is important. And then I think lastly and ultimately when we're talking about a neoadjuvant approach, you want to ask your treating oncologist, "Would it be better to give my treatment before surgery or after surgery?" And really discuss the pros and cons with the physician and have them incorporate all of the factors that go into these treatment decisions. How well you'll tolerate chemotherapy, other medical conditions that may play a role in the likeliness of getting through those treatments safely, perhaps underlying diseases that may increase the risk of immune-related side effects with immunotherapy. You really want to factor in all of these things and discuss the pros and cons of a systemic treatment first versus surgery first before making final decisions on how to treat locally advanced lung cancer. All right. Thank you. ASCO: Thank you, Dr. Gentzler. Next, Dr. Aggarwal will discuss what people with early-stage non-small cell lung cancer should know about their adjuvant treatment options for after lung surgery.   Dr. Aggarwal: This is Dr. Charu Aggarwal. I'm the Leslye Heisler Associate Professor for Lung Cancer Excellence at University of Pennsylvania's Abramson Cancer Center. And today I will talk to you about the use of adjuvant immunotherapy in the setting of early-stage non-small cell lung cancer. We'll start by discussing what adjuvant therapy is, what types of options we have for adjuvant therapy, what kind of testing is important, and what options there may be in terms of adjuvant immunotherapy. So let's get started. Early-stage lung cancer comprises of stages between stage I to stage III. These stages vary by the size of the tumor as well as the level of lymph node involvement. In the setting of very early-stage lung cancer, such as stage I and stage II, as well as some select stage III lung cancers, we recommend surgical resection. And in these patients, the use of additional treatment is recommended based upon the pathological determination of the tumor size as well as the lymph node status. If usually lymph nodes are involved, we recommend adjuvant chemotherapy, and also, many experts will deliver adjuvant chemotherapy for tumors that may be larger than 4 centimeters even in the absence of lymph node involvement. The data for adjuvant chemotherapy comes from several large clinical trials that were conducted about a couple of decades ago now that demonstrated not only an improvement in preventing recurrence of the cancer but also a modest improvement in overall survival, really laying the ground for improvement and therefore becoming the gold standard. Four cycles of chemotherapy are usually administered about 6 to 12 weeks following surgical resection, and this is really the basis of our treatment in the early-stage setting. In today's time and age, we now have several other options. We have treatment options that include molecular therapy, which is biomarker driven, as well as the use of immunotherapy. So it's actually very important for us in the adjuvant setting--or in the post-surgical setting--to test for mutations such as EGFR. It's also important for us to test PD-L1 status. So let's dive into why each of these may be important. Patients with EGFR mutations, especially those with sensitizing mutations in EGFR exon 19 or 21, now have the opportunity to receive a targeted therapy in the form of osimertinib, which is an oral drug, very targeted and specific for the EGFR mutation that has been studied in a clinical trial setting in patients with early-stage non-small cell lung cancer. In patients with stage IB to IIIA non-small cell lung cancer with EGFR mutation, use of osimertinib was associated with a significant improvement in our ability to delay the recurrence of cancer. Based on this significant improvement, FDA approved therapy with osimertinib, and it is currently available and ready to use. We usually recommend it for 3 years, so daily therapy for 3 years, and patients are monitored with routine CAT scans and lab work. For patients who don't have an EGFR mutation, we do recommend broad panel testing. Of course, this is not the standard, but I think it's important for us to identify patients who may not benefit from immunotherapy. Patients that have an ALK mutation, for example, or ROS1 translocation, may not have the best chances of responding to adjuvant immunotherapy, and therefore, I think testing should be performed to make sure that we are having a shared decision-making conversation with our patients about the use of the correct adjuvant options. In terms of adjuvant immunotherapy, we now have 2 approved agents. One of them is atezolizumab, and the other one that was just recently approved is pembrolizumab. Atezolizumab was approved on the basis of a large clinical trial called the IMpower010 study, which randomized 1,280 patients with stage IB to IIIA non-small cell lung cancer to either 1 year of atezolizumab or best supportive care. Of note, all of these patients had to have had adjuvant chemotherapy that included a cisplatin platinum chemotherapy. In the first analysis, we found that the disease-free survival or the probability of the patients remaining cancer-free was significantly improved in those patients that had a tumor expression of PD-L1 greater than or equal to 1% and received atezolizumab compared to patients who did not receive atezolizumab. On the basis of this positive primary endpoint, the U.S. FDA approved the use of adjuvant atezolizumab for patients with stage II to IIIA resected non-small cell lung cancer after surgical resection and adjuvant chemotherapy. Recently, we heard that this does lead to small but significant improvement in overall survival. There is a trend towards improvement in overall survival. However, the data are quite immature at this point, and we do need longer follow-up to be able to follow this trend. The greatest magnitude of overall survival benefit was found in patients who had the PD-L1 greater than or equal to 50%. So it's important to know what the PD-L1 level of a patient may be when I'm thinking about adjuvant immunotherapy because adjuvant immunotherapy is most likely to benefit those that don't have an actionable mutation, such as EGFR, and those that have the highest PD-L1 staining, at least in the IMpower trial. Secondly, the PEARLS clinical trial is a clinical trial that evaluated the use of pembrolizumab, which is another immunotherapy agent, again, in the adjuvant setting. For this clinical trial as well, there was a small but significant improvement in disease-free survival, again preventing the probability of recurrence in all patients that received pembrolizumab compared to the best supportive care. And basically, this led to also an approval by the FDA for the use of pembrolizumab. Again, now we have 2 options. Both of these are administered for 1 year. What should patients know about therapy? These drugs are usually administered once every 3 weeks. They are given intravenously. Sometimes, we can change the treatment schedule to be either once every 4 weeks in the case of atezolizumab or every 6 weeks in the case of pembrolizumab. These may be associated with some side effects. Immunotherapy side effects that are most common are fatigue, chills, myalgias, or basically a feeling of pains in the body or joints. But also, some serious life-threatening reactions can occur such as activation of the immune system to such an extent that the immune system may start to attack the body's organs. So this may lead to swelling or inflammation in the organs that may manifest itself as colitis if the gut gets inflamed, or pneumonitis if the lungs were to get inflamed, or pancreatitis if the pancreas were to get inflamed. Any organ in the body can really get inflamed. We've certainly seen cases of thyroiditis. We've seen cases of polyarthritis. We've seen cases where the brain may also get inflamed or the pituitary may get inflamed. So there are definitely some life-threatening reactions or side effects that can occur with the use of immunotherapy that should be closely monitored. The benefit of having used immunotherapy in the metastatic setting is that now we have a lot of experience managing these side effects. And if recognized early, these side effects can be managed appropriately with the use of steroids as well as holding therapy. Many of the times, we can even reinstitute immunotherapy without significant harm to the patients. However, I think immunotherapy benefits as well as side effects should be discussed in detail with the provider, especially in the adjuvant setting. Patients may ask if neoadjuvant immunotherapy along with chemotherapy is a better approach compared to adjuvant immunotherapy. At this time, we don't have a clinical trial that is comparing neoadjuvant chemoimmunotherapy followed by surgery to an approach that is surgery followed by adjuvant immunotherapy. In general, I would say that if the decision by a multidisciplinary team has been made to proceed with surgery, careful discussion should be had about adjuvant chemotherapy as well as the use of adjuvant immunotherapy, and molecular testing should be performed. All patients with early-stage disease should have a multidisciplinary tumor board discussion, which includes engagement with surgeons, radiation oncologists, pulmonologists, pathologists, and medical oncologists so that they can ensure that many experts have had the chance to weigh into their case as well as come to the right conclusion on whether or not to use new adjuvant chemoimmunotherapy or just to proceed with surgical resection. ASCO: Thank you, Dr. Aggarwal. You can learn more about neoadjuvant and adjuvant treatment options for early-stage non-small cell lung cancer at www.cancer.net/lung. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.   And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.  Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate. 

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. The theme of the 2023 ASCO Annual Meeting was “Partnering With Patients: The Cornerstone of Cancer Care and Research.” From June 2 to 6 in Chicago, Illinois, and online, cancer researchers and clinicians from around the world gathered to discuss the latest cancer research and how to ensure that all people receive the cancer care they need. In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field presented at the meeting and explain what it means for people with cancer. In today's episode, our guests will discuss new research advances in treating non-small cell lung cancer, small cell lung cancer, and mesothelioma.  Dr. Charu Aggarwal is the Leslye Heisler Associate Professor of Medicine in the Hematology-Oncology Division at the University of Pennsylvania's Perelman School of Medicine in Philadelphia, Pennsylvania. She is also the 2023 Cancer.Net Associate Editor for Lung Cancer. Dr. Melina Marmarelis is an assistant professor at the University of Pennsylvania, the Medical Director of the Penn Medicine Mesothelioma Program, and the co-director of the Molecular Tumor Board at the University of Pennsylvania. She is also the 2023 Cancer.Net Specialty Editor for Mesothelioma. Dr. Kristin Higgins is a radiation oncologist, Professor and Vice Chair in Clinical Research in the Department of Radiation Oncology at Emory University School of Medicine and medical director of radiation oncology of The Emory Clinic at Winship Cancer Institute's Clifton campus location. She is also a 2023 Cancer.Net Advisory Panelist for Lung Cancer. You can view disclosures for Dr. Aggarwal, Dr. Marmarelis, and Dr. Higgins at Cancer.Net. Dr. Aggarwal: Hello and welcome to this Cancer.Net Research Round Up podcast. Today, we will be talking about the latest research from the Annual Meeting of the American Society of Clinical Oncology from June 2023, and I'm joined today by 2 experts in the field of lung cancer. Before I introduce them, I'd like to introduce myself. I'm Dr. Charu Aggarwal. I'm an associate professor for lung cancer excellence at the University of Pennsylvania's Abramson Cancer Center. I'd now like to introduce Dr. Melina Marmarelis. Dr. Marmarelis: Hi, so happy to be here. I'm Melina Marmarelis. I'm an assistant professor at the University of Pennsylvania and the medical director of the Penn mesothelioma program. Dr. Aggarwal: And Dr. Kristin Higgins. Dr. Higgins: Hi, everyone. I'm Kristin Higgins. I am a thoracic radiation oncologist at Winship Cancer Institute of Emory University. I'm a professor and vice chair for clinical research for radiation oncology. Dr. Aggarwal: Fantastic. So today, we'll talk about relevant research as it applies to practical implications in the clinic for practitioners, but most importantly, patients with lung cancer. I'd like to start off by discussing 2 key studies, and I would love for perspectives from our faculty here. The first study I want to highlight is the ADAURA trial. This is a trial that has already sort of changed practice in most recent years when the study was presented at the Annual Meeting of the American Society of Clinical Oncology in 2020, but we have new updates on this study as of 2023. So, in brief, this was a study that looked at the value of administering an oral pill called osimertinib that is a tyrosine kinase inhibitor against the EGFR, or the epidermal growth factor receptor, in patients with non-small cell lung cancer. We know that non-small cell lung cancer is quite a heterogeneous disease with some subsets of patients having mutations that may render them increasingly sensitive to the effects of these tyrosine kinase inhibitors. In fact, these pills have been used in the metastatic setting for several years based on an improvement in overall survival. What the ADAURA study tried to do was ask the question if this pill would add an incremental advantage after receiving curative-intent surgical resection in those with early-stage lung cancer. So this study enrolled patients with stage IB to IIIA non-small cell lung cancer after surgical resection and focused only on those patients that had sensitizing EGFR mutations with EGFR exon 19 deletion or L858R mutations. Patients could receive chemotherapy after having the surgery and then were basically randomized into 2 groups, one of whom received osimertinib at a dose of 80 milligrams once daily for a total of 3 years. Patients were followed up for recurrence. We already know from the earlier results that patients who received osimertinib had a better chance of delaying the recurrence of disease. However, what we found at the Annual Meeting this year is that the administration of this osimertinib also improved overall survival, which is really what we all look for in the oncology world. If you're administering a therapy, especially for a long duration, we want to be able to see a survival benefit, and that's what we saw. In fact, in patients who received osimertinib, there was a 49% less likelihood of dying from lung cancer compared to those who did not receive osimertinib. This, I think, is practice-affirming. It may not be practice-changing because some of the practitioners started using osimertinib after its FDA approval in December of 2020, but I think it just confirms our practice as it delivers an overall survival advantage in these patients. One thing that's increasingly important is to identify patients who have this mutation, so now we have efforts underway locally as well as nationally to perform molecular genotyping on all patients with lung cancer so that we can adequately and appropriately treat those with early-stage lung cancer following curative resection or following surgery. Melina and Kristin, what are your thoughts? Dr. Marmarelis: Well, I think these results are really important because it did, as you say, affirm kind of what we're already doing, but I think the most convincing part of this for me is the prevention of spread of disease to the brain. This is not comparing osimertinib after surgery versus osimertinib ever, which I think is a difficult part about interpreting this trial. But I think the fact that it prevented disease from going to the brain is really meaningful to everyone, to patients, to the physicians that are caring for them, so I think that's a really important endpoint. Dr. Higgins: I agree with Melina. I think this is really exciting for our patients. It's exciting to have more treatment options for early-stage lung cancer. I think patients that are diagnosed with early-stage lung cancer are highly motivated to do everything they can to improve their likelihood of being cured. So I tend to have a lot of conversations about side effects and toxicities with patients that have questions and are sort of wondering how it will affect their quality of life, and of course, that is an important piece of it because patients that do have curable lung cancer are probably starting off with a better overall quality of life, but I think generally speaking, our patients have tolerated it well. I'm also kind of excited from a radiation oncology point of view. We treat patients with stereotactic body radiation therapy [SBRT] that are medically inoperable. And we have another trial with a cohort looking at osimertinib for those patients that have EGFR mutations, too, and that's ongoing, again, applying the same concept of trying to really use these SBRTs that work really well in the advanced setting, moving them into earlier stages of disease to help us care for more patients. So overall, I think it's really exciting, and I think it's a huge win for the clinical research community. Dr. Aggarwal: Well, that's wonderful. And I think this certainly advances the field as this is the first targeted therapy approved for patients with early-stage non-small cell lung cancer. I should add that AstraZeneca, the company that makes this drug, has provided institutional research funding to my institution, and I also serve as an advisor to them, but I was not involved personally in the research of this clinical trial. I'd like to move on but stay within the field of early-stage lung cancer and talk about another study called the KEYNOTE-671 study, and this is important because it really applies the idea of using immunotherapy before and after surgical resection in patients with early-stage lung cancer. Just to give a little bit of background to our listeners, we now have 3 approvals for the use of immunotherapy in patients with early-stage lung cancer. Two of those are in the adjuvant setting, meaning that if a patient undergoes surgical resection or surgery for early-stage lung cancer, they can receive either atezolizumab or pembrolizumab following that surgery, and that has been shown to improve outcomes in terms of reducing the chances of recurrence. We also have another approval, which is the third approval in early-stage lung cancer, where 3 cycles of chemotherapy and immunotherapy are administered prior to surgery, also called as the neoadjuvant chemo-immunotherapy approach. This drug that has been approved in combination with chemotherapy is nivolumab, and this approval came from a clinical trial called CheckMate 816 that showed both that patients who received this neoadjuvant chemo-immunotherapy approach had a higher proportion of patients who had complete response or pathologic complete response in their tumors at the time of surgery and also showed that the chances of the disease coming back after surgical resection was much lower amongst those that had received this intervention. The current study, the KEYNOTE-671 study, builds upon this concept and adds both a before-surgery intervention as well as an after-surgery intervention. So what this study did was it enrolled patients with early-stage, stage II to IIIB non-small cell lung cancer, and patients in the intervention arm received 4 cycles of chemotherapy in combination with pembrolizumab, underwent surgery, and then received immunotherapy with pembrolizumab for up to 13 cycles. Patients in the control arm received only chemotherapy prior to surgery and then placebo for up to 13 cycles after. This was a large study with about 786 patients randomized, and what we found was that those patients that received the intervention had a much higher likelihood of remaining disease-free or event-free following surgical resection as well as in the early analysis, an improvement in overall survival with about a 27% reduction in the risk of death. So I do think that this is the first study that shows us that use of both neoadjuvant as well as adjuvant. So sort of this perioperative approach of using immunotherapy before and after surgical resection can actually lead to improved outcomes. This is ultimately what we want for our patients, improvement in overall survival, improvement in cure rates, etc. The study has been silent on the use of radiation therapy, although it has gone into details in terms of the kinds of surgery that was done. Kristin, what are your views about this? Dr. Higgins: I think postoperative radiation after resection for non-small cell lung cancer has sort of started to fall out of favor because of the Lung ART trial that was published in Europe, a randomized phase III trial that showed no differences in disease-free survival or overall survival. And that's not to say that there aren't more study questions on ways to give it safer and ways to incorporate radiation in with the chemo-IO approach, and there are some novel ways to do that, and we're going to see some data presented at the World Lung Cancer Conference looking at some of those novel approaches. But standardly, when patients receive neoadjuvant chemo-immunotherapy followed by surgery, we typically would not offer radiation. There are instances, though, when patients have positive margins, for example, and in that situation, it's sort of a discussion on a case-by-case basis. But ideally, we're hoping that most of these patients that go to surgery are able to get a complete resection, and that's really the key component of the decision-making for deciding if patients are eligible for this approach. Dr. Aggarwal: I agree. Melina, any additional thoughts on this trial? Dr. Marmarelis: I think it's an exciting trial for the reasons that you mentioned. I think it does bring up a number of questions about whether both neoadjuvant and adjuvant immunotherapy are needed. I tend to like the idea of having immunotherapy present when the tumor is present before surgery, so I like kind of having that on board, but I think we still don't know which is more important. Dr. Aggarwal: So it certainly raises many more questions, which hopefully will be answered in the future. KEYNOTE-671 trial was conducted by Merck that produces the drug Keytruda, or pembrolizumab. We have received institutional research funding for other trials. I was not personally involved in this clinical trial. I do serve as an advisor for Merck. I think we'll bring you more research from the ASCO Annual Meeting. And I'll turn it over to Dr. Marmarelis to discuss some more exciting research. Dr. Marmarelis: Thanks, Charu. So perhaps it's not surprising that one of the exciting things I picked from ASCO has to do with mesothelioma. And I just want to put into context a little bit about why this trial was important. This is IND227. It was a cooperative group trial done across Canada, France, and Italy, and this was chemotherapy plus or minus pembrolizumab in patients with pleural mesothelioma that did not undergo surgery. So this was their first treatment, and they were not undergoing surgery. And the reason this trial was important is that in the last few years, we had results from CheckMate 743, which was looking at IPI/NIVO, so a combination of immunotherapies versus chemotherapy. And there was an improvement in survival for those that received double immunotherapy, and that improvement was most pronounced in the non-epithelioid population, which is actually a smaller subset of pleural mesotheliomas. And so as we've seen in the lung when we look at immunotherapy versus chemo, it raises the question of whether combination immunotherapy plus chemotherapy would actually be better for all and, in particular, for all histologies in pleural mesothelioma. So this was looking at that concept. It took the standard chemotherapy, carboplatin-pemetrexed or cisplatin-pemetrexed, and then combined it with one immunotherapy, so slightly less than the combo immunotherapy seen in CheckMate 743, and that was pembrolizumab. And what they saw was that there was a small overall survival improvement in the group that got pembrolizumab. Again, that was most pronounced in patients in the non-epithelioid group, so those with sarcomatoid or biphasic histology. And this is really a prelude to several other trials that are coming out in mesothelioma, namely the DREAM3R trial, which is looking at chemotherapy plus or minus durvalumab. That control arm also includes IPI/NIVO, so that will be really important to be able to compare those, and then also the BEAT-meso trial, which is looking at chemotherapy-immunotherapy but also with an anti-VEGF agent, bevacizumab. So I think this was an important trial. It's a little bit of proof of concept, but there's still a lot that we're looking forward to. It's not quite practice-changing in the clinic, although I think it's certainly an option that people are using, but I'm looking for more data going forward. Dr. Aggarwal: It's incredible to see how far we've come in mesothelioma within the last decade. We are introducing immunotherapy. We're introducing novel agents in the first-line setting. Dr. Marmarelis: The other trial that I was interested in was KEYNOTE-789, which is looking also at patients with EGFR mutations and those that had the original osimertinib as their first-line treatment or another tyrosine kinase inhibitor and then had disease progression on that TKI. And this is an area of huge need. We have patients that do really well on targeted therapies, and then they have disease progression, and we're looking for additional targeted options, but we're also looking for effective chemotherapy options. And one of the questions that has risen from this is whether there's a role for immunotherapy. We know that immunotherapy alone in patients with EGFR mutations is not very effective when you look at a broad population, but in combination with chemotherapy, it's possible that it can add some benefit. So this trial looked at those that had EGFR mutations, had disease progression after a targeted therapy, and then it randomized them to chemotherapy plus or minus pembrolizumab, so chemotherapy plus or minus immunotherapy, and interestingly, it had no difference in the progression-free survival or the overall survival. So the 2 arms were really similar in terms of outcomes. There was also no difference in the overall response rates of the amount that the drug actually shrinks the tumor. So it really doesn't look like immunotherapy is adding much to chemotherapy for these patients. I think we still need to look a little bit closer because there are probably some patients with EGFR mutations that could benefit from immunotherapy, but we're really not very good at identifying those. One of the questions that comes up in this space is whether to add anti-VEGF treatment in addition to chemotherapy and immunotherapy. So there are some upcoming trials looking at that. Dr. Aggarwal: I think this was a trial that was actually very important and again, practice-affirming that this idea of continuing chemotherapy without adding immunotherapy, patients are not losing much. In fact, they're not gaining anything by adding immunotherapy as shown in this clinical trial. I think continuing immunotherapy, so continuing osimertinib, may be important in this setting also because we know that osimertinib can cross the blood-brain barrier. It can provide that CNS [central nervous system] protection. Dr. Marmarelis: Yeah, I think that's a great point that the comparison here is not chemotherapy plus osimertinib. It's chemotherapy alone. So I agree that the control arm is not quite what some of us do. I agree. I do the same as you do. I also just want to mention that the KEYNOTE trial and the previous trial about mesothelioma used pembrolizumab, which is made by Merck. We have received institutional funding, and I've served as an advisor as well as received honorarium from Merck.   Dr. Aggarwal: Melina, those were 2 very important studies and certainly, I think, answer some very relevant questions in clinic in the management of patients with EGFR-mutant lung cancer, for example. And then I think we look forward to more practice-changing data in mesothelioma. Kristin, I would love to hear research from ASCO from you. What caught your interest? Dr. Higgins: So I have a special interest in small cell lung cancer. And I think there was one important small cell lung cancer trial that I wanted to review with everyone. It was SWOG S1929. And SWOG is the Southwest Oncology Group, and it's a cooperative group that conducts clinical trials in cancer funded by the National Cancer Institute. And this is a randomized phase II trial of atezolizumab and chemotherapy followed by randomization to continuing the maintenance of atezolizumab with a PARP inhibitor. Now, we know from prior data that PARP inhibition is attractive for small cell lung cancer because PARP is expressed frequently in small cell lung cancer, and there is a biomarker called Schlafen-11 that preclinical data and prior data has shown can predict response to PARP inhibition. And this trial was sort of a proof-of-concept trial, a small, randomized phase II trial testing whether or not that Schlafen-11 biomarker could be used to direct therapy. Now, in this trial, there were 309 patients that were registered. They then had to have their tumor samples sent for central testing for the Schlafen-11 expression. One thing that I think is important to bring up is that in small cell lung cancer, there's this belief that it's really hard to get tissue samples from small cell lung cancer and it's a difficult thing logistically because it's just a lot harder to access these tumors. But interestingly, in this trial, 80% of patients had tumors that were evaluable for the biomarker, and the median time to the test result was only 7 days. So patients were able to get their tumor tested, get it sent out, get results in a rapid manner, and then be randomized based on these results. The primary endpoint for this trial was progression-free survival, and the primary endpoint was met. Progression-free survival was 4.2 months versus 2.8 months. Now, I think many people will say the magnitude of benefit here is not very much, but it's small cell lung cancer, and we don't have a lot of positive trials in this space, and we also don't have many trials that have used a biomarker to direct therapy. So I think for those reasons, it's really exciting to see these results. It was also conducted within a cooperative group with multiple different sites across the United States, and the fact of the matter is that we can do trials like this in small cell lung cancer patients, and I think it will sort of serve as a precedent for future trial design. Now, the overall survival for the trial is still premature. It didn't look that much different with the PARP inhibitor, but that doesn't mean that, again, things could change with more follow-up. And I really like the approach of this trial design, and I'm excited to see biomarker-driven trials in small cell lung cancer. Charu and Melina, what do you guys think about this study? And what do you think about our small cell lung cancer patients and our ability to conduct future trials like this? Dr. Aggarwal: I think this is certainly an advance. As you pointed out, Kristin, it shows us that we can conduct trials in the space. I think it offers a lens into the potential of personalized therapy in small cell lung cancer, which has eluded us for a very long time. The standard of small cell lung cancer has not changed significantly for a very long time, so I think this is very exciting and can't wait to see more things come in the future. Dr. Marmarelis: Yeah, I agree. I think we've always been asking for additional biomarkers, especially in such a difficult disease like small cell. And so this is really exciting to see potential biomarkers and that it was feasible to actually pose that question and study it. So that part's really exciting. Dr. Higgins: Great. And I should also say I was not involved in the study, and I'm not associated with any of the pharmaceutical companies that were involved in the study for S1929. And the final study that we wanted to talk about was the phase III LUNAR study, and this is sort of a different type of trial in the setting of advanced non-small cell lung cancer. It was studying tumor treatment fields with standard of care in metastatic non-small cell lung cancer after progression with platinum-based therapies. And first, I just want to step back and explain what tumor treating fields are. Tumor treating fields are applied to a patient with a transducer that's placed on the skin, and what it does is it applies an electrical field, and that disrupts mitosis when the cancer cells are trying to divide. And the mechanism of cell death is a little bit unclear. There are sort of many mechanisms that are postulated, one of which is immunogenic cell death, but we don't really know, I think, what's happening. But there have been studies that show improved results with tumor treating fields and other diseases. For example, particularly in glioblastoma multiforme, tumor treating fields are used in combination with surgery, radiation, and temozolomide (Temodar). So it's something that's being used in other disease sites, and this is some of the early data that we've seen in metastatic non-small cell lung cancer. And so in this trial, 276 patients were randomized to tumor treating fields plus standard of care or standard of care alone. Now, I should mention that this trial began enrolling patients in 2016, and so the standard of care was very different. After platinum-based therapies, the standard was considered docetaxel. Of course, platinum-based therapy alone for frontline treatment of advanced non-small cell lung cancer is also not the standard of care anymore. And so I think with that in the background, it does make interpretation of these results somewhat difficult, and that's probably the major caveat to this study. But nonetheless, patients were randomized, 276 patients. The primary endpoint of the study was overall survival. They were looking at progression-free survival and overall response rates as secondary endpoints as well as overall survival in patients that received immunotherapy versus just chemotherapy alone. And the trial was positive. Overall survival was improved. The median overall survival was 13.2 months for patients that received tumor treating fields with standard of care versus 9.9 months for standard of care alone. If you look at 3-year survival, it was 18% versus 7%. I think this is a new type of therapy for our patients with non-small cell lung cancer. It is somewhat of a difficult thing to wear the transducer, and you have to wear it for many, many hours. So that is one thing that I think can be difficult for patients that are using this treatment, but nonetheless, it is something new for advanced non-small cell lung cancer. I do know that the technology of tumor treating fields is being studied in other settings for non-small cell lung cancer, for stage III non-small cell lung cancer, for example, and also in the frontline setting. I think this trial kind of speaks to the fact that the landscape of advanced non-small cell lung cancer is changing so rapidly, and when we're studying something novel, we have to make sure that we make these trials feasible for enrollment so that we can get them completed rapidly, and we can get a readout and it doesn't become obsolete based on this shift in the standard of care. So I think it just really kind of drives home that we need to make sure that we're taking that into account with trial design. It's not standard of care changing right now, but it'll be interesting to see how the data evolves over time. Melina, I'm interested to hear your point of view because I know that these can be used in mesothelioma, maybe not that frequently. What is your experience with tumor treating fields, if any? Dr. Marmarelis: Tumor treating fields are approved as a device in pleural mesothelioma in the first-line setting in combination with chemotherapy. They have been used off-label in other settings, but that's the device approval. The trial that looked at tumor treating fields in mesothelioma was a single-arm trial, so there was no control arm, and it was really actually just looking at the safety of the device. So I have not used it personally in mesothelioma, although I know of patients and I know of real-world studies looking at its use, and I think it's potentially an interesting modality of treatment, especially in combination with immunotherapy, given that it really doesn't have a lot of additive toxicity. But I think the question is really, which patients are benefiting from it, and which patients are able to actually wear the vest in the case of mesothelioma? Dr. Higgins: Yeah. Any thoughts, Charu? Dr. Aggarwal: I agree, and I think this is going to be largely driven by patient experience. I think this is going to be quite onerous to wear this, carry the suitcase, so I would be very interested in patient reported outcomes as well as patient experiences and stories, which will really drive our use here. Dr. Higgins: Yeah, that's a great point. I should say that this trial was sponsored by Novocure. My institution does have other Novocure studies underway, and we receive research funding, but I was not involved in the study, and I did not personally receive any research funding. Dr. Aggarwal: Thank you, Kristin. This has been a wonderful review of practice-changing and some promising research that came out of the ASCO Annual Meeting. I hope our listeners enjoyed it, and we'll be sure to update you with the next annual research conference. Thank you, everyone. ASCO: Thank you, Dr. Aggarwal, Dr. Marmarelis, and Dr. Higgins. You can find more research from recent scientific meetings at www.cancer.net. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care. And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

Please visit answersincme.com/ZRV860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, two experts in lung carcinoma discuss the latest data in first-line chemoimmunotherapy for non–small-cell lung cancer.Upon completion of this activity, participants should be better able to: Outline which patients might align with first-line chemoimmunotherapy regimens for advanced NSCLC; Review the clinical profiles of chemoimmunotherapy regimens in the first-line setting for the treatment of advanced NSCLC; and Translate the latest data informing the use of first-line chemoimmunotherapy regimens to individualized care of patients with advanced NSCLC.

Caris Precision Oncology Alliance™ Chairman, Dr. Chadi Nabhan, sits down with Dr. Charu Aggarwal, the Leslye M. Heisler Associate Professor for Lung Cancer Excellence at UPENN, and Dr. Balazs Halmos, Director, Thoracic Oncology at Montefiore. Together they discuss adjuvant and neoadjuvant therapy for resected non-small cell lung cancer (NSCLC). Topics discussed will include current treatment options, how treatment decision are made, and when treatment should be given. For more information, please visit: www.CarisLifeSciences.com/POA-Intro/

Discussing Lung Cancer ASCO 2023 Highlights, focusing on practice-changing studies with Dr. Charu Aggarwal, Director, Precision Oncology Innovation, Associate Professor of Lung Cancer Excellence at Penn Medicine. Covering three important studies: - ADAURA trial update with increased OS with adjuvant Osimertinib - KEYNOTE 789 - Pemetrexed and platinum with or without pembrolizumab for tyrosine kinase inhibitor (TKI)-resistant, EGFR-mutant - KEYNOTE 671 - Randomized, double-blind, phase 3 study of pembrolizumab or placebo plus platinum-based chemotherapy followed by resection and pembrolizumab or placebo for early stage NSCLC

Within the last few years, an “explosion of data” regarding adjuvant and neoadjuvant treatment for resectable lung cancer has contained “major wins” for patient care. Although exciting, the rapid advancement has led to questions about when chemotherapy and chemoimmunotherapy should be adopted or avoided. Bob Figlin, MD, the Steven Spielberg Family Chair in hematology-oncology at Cedars Sinai Cancer in Los Angeles, and Charu Aggarwal, MD, MPH, the Leslye M. Heisler Associate Professor for Lung Cancer Excellence at the University of Pennsylvania's Abramson Cancer Center in Philadelphia, discuss how to apply key recent findings. They also share “the special sauce” that allows Dr. Aggarwal's team to make the best determination for surgical timing.  

Discussing the management of Localized Non-Small Cell Lung Cancer (NSCLC) using the algorithm – with Dr. Charu Aggarwal, Associate Director - Penn Center for Precision Medicine, Associate Professor for Lung Cancer Excellence. Website: http://www.oncbrothers.com/  Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com

In this episode of Lung Cancer Considered, host Dr. Stephen Liu leads a recap of the recent IASLC meeting, Targeted Therapies for Lung Cancer, or TTLC23 --a member-favorite, a relatively smaller meeting known for its fast pace and its breadth of content. Guests include, the two co-chairs of the meeting: Dr. Charu Aggarwal, thoracic medical oncologist at the Hospital of the University of Pennsylvania and the Leslye M. Heisler Associate Professor for Lung Cancer Excellence at the University of Pennsylvania. Dr. Joel Neal, thoracic medical oncologist and Associate Professor at Stanford University where he is also the Medical Director for the Cancer Clinical Trials Office.

Over the past few years, the use of liquid biopsy has improved the ability to detect biomarkers for non-small cell lung cancer. In this episode of Lung Cancer Considered, host Dr. Stephen Liu leads a discussion on the current state of liquid biopsies with Dr. David Gandara, Professor of Medicine and Director of Thoracic Oncology at the University of California, Davis; Dr. Charu Aggarwal, the Leslye M. Heisler Associate Professor for Lung Cancer Excellence at the University of Pennsylvania; and Dr. Christian Rolfo, Professor of Medicine at Mount Sinai in New York City and the Associate Director for Clinical Research in the Center for Thoracic Oncology at the Tisch Cancer Institute.

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. In the Research Round Up series, ASCO experts and members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's episode, our guests will discuss new research in lung cancer, lymphoma, and childhood cancer that was presented at the 2022 ASCO Annual Meeting, held June 3-7 in Chicago, Illinois. First, Dr. Charu Aggarwal will discuss 3 studies looking at treatment options for people with non-small cell lung cancer. Dr. Aggarwal is the Leslye Heisler Associate Professor of Medicine in the Hematology-Oncology Division at the University of Pennsylvania's Perelman School of Medicine in Philadelphia, Pennsylvania. She is also the Cancer.Net Associate Editor for Lung Cancer. You can view Dr. Aggarwal's disclosures at Cancer.Net. Dr. Aggarwal: Hello and welcome to this Cancer.Net podcast. I'm bringing you updates from the Annual Meeting of the American Society of Clinical Oncology, held in Chicago in 2022. I'm Dr. Charu Aggarwal. I'm the Leslye Heisler Associate Professor for Lung Cancer Excellence at the University of Pennsylvania's Abramson Cancer Center. I will be discussing updates on 3 studies today that offer insights and new advances in the management of patients with non-small cell lung cancer. I don't have any direct relationship with any of these companies or studies, and you can view a list of my disclosures on the Cancer.Net website. First off, I would like to talk a little bit about advances in the management of patients with EGFR exon 20 mutations. We know that a lot of advances have been made in the management of patients with non-small cell lung cancer, and much of that has been attributed to the fact that we are now able to deliver targeted therapy for a subset of patients. EGFR mutations form one such subset where we have a lot of oral drugs that are available, and we can offer these that improve survival, and patients can avoid chemotherapy, immunotherapy, and other IV infusional therapies. Within the subset of EGFR mutations lies this unique subset of EGFR exon 20 insertion mutations, which have been historically harder to target with currently available EGFR inhibitors. And over the last 5 years, we have seen tremendous growth of opportunities, targets, and new drugs for this subset of patients. The mutations in this subset forms about 2% to 5% of all non-small cell lung cancers. But now we have 2 FDA-approved drugs in this space, one being intravenously administered, amivantamab, and another that is orally available, mobocertinib. We covered this in a podcast as well as a blog, so please check those out on our Cancer.Net website. But building upon that progress, there is now another drug that was reported at ASCO. This drug is called CLN-081. And we saw preliminary activity in a phase 1 and 2 study of this molecule or this drug in patients with EGFR exon 20 insertion mutations. It's an orally available drug. The top line data is that it is safe, it is effective, it was tested in different doses. It was tested at less than 65 milligrams, 100 milligrams, and 150 milligrams, again, as I mentioned, administered orally, and we saw responses and patients that had previously received other therapies and may have progressed on other therapies. And what we found was that this drug also tends to have activity against brain metastases, which I think is this huge unmet need in the management of such patients. So I think more to come, but again, I think offers us an insight into what may be in the future, an attractive drug for our patients with EGFR exon 20 insertion mutations. So stay tuned, more on that in the future. Shifting gears, I would like to now talk about one of the common mutations. So we talked about EGFR exon 20, which is about only 2% to 5%, but the largest subset of mutations in non-small cell lung cancer really revolves around KRAS mutations, and these form about 30% to 35% of all mutations in non-squamous, non-small cell lung cancer. And amongst this group there is another subset which is KRAS G12C non-small cell lung cancer, that forms about 13% of all lung cancers. We have 1 approved drug already in this space by the name of sotorasib that is FDA approved for the management of patients with this particular mutation after having received 1 prior therapy, be it chemo-immunotherapy or immunotherapy. At this year's ASCO meeting, we heard data from a study called KRYSTAL-1, which looked at the activity and safety of another molecule called adagrasib, which is an orally available drug targeting KRAS G12C, again, in a similar population of patients with advanced and metastatic non-small cell lung cancer harboring a mutation. We found that this drug is again effective, the overall response rate was about 43%, the majority of the patients had stabilization of disease, about 80%, and many patients were able to remain on treatment with stabilization of disease. We found that this drug does have side effects and adverse events and most commonly of this were diarrhea, nausea, vomiting, and fatigue. Many patients did require dose reductions, but the activity of the drug remained despite dose reductions. Now, what would be the advantage of this drug against the currently available sotorasib? In another smaller study reported at ASCO, there seemed to be activity in the brain, including intracranial penetration with the use of this molecule, adagrasib, which has not been demonstrated before with other KRAS G12C inhibitors, so I think that makes it a potentially attractive option. Again, I will say that the report of this intracranial activity was in a very small subgroup of patients, so I think needs to be further corroborated in a larger study. Shifting gears again and talking about our last study, so I would like to highlight what do we do if, in case, patients don't have a targetable mutation. I want to highlight that we do have a lot of available options, and we are continuing to improve upon available options. The way we treat such patients is by using immunotherapy, either alone or in combination with chemotherapy. But what do we do after this treatment stops working? Researchers from the Southwestern Oncology Group, or SWOG, launched a massive national effort called Lung-MAP, which is basically a clinical trial that evaluates several different strategies all at once, either for patients with targetable mutations or for patients without a targetable alteration. And they reported results from a study that evaluated the combination of pembrolizumab with ramucirumab in patients that may have progressed after frontline immunotherapy. Now, pembrolizumab is immunotherapy, so the concept was, can we continue immunotherapy beyond progression and perhaps get some synergistic activity by using ramucirumab, which is a drug that prevents blood vessels from forming in the tumor itself. It's an anti-angiogenic agent, meaning that it is a targeted molecule that prevents blood vessel formation and promotes tumor death. What they found was that patients that received pembrolizumab and ramucirumab were more likely to live longer, so overall survival was longer for patients with this combination compared to a physician investigator discretion choice, such as chemotherapy in combination with ramucirumab or other chemotherapies that are otherwise used in the second line setting. And interestingly, we did not find a significant improvement in shrinkage with this combination of pembrolizumab and ramucirumab or a significant reduction in the time of progression-- or, sorry, prolongation of the time of progression of disease. But the overall survival findings are interesting, and I think that's why we are including them in this podcast because that's one of the approaches that is leading to an improvement in survival and improvement in outcomes. I will point out that this is a phase 2 study. These results would need to be validated in a large prospective phase 3 trial so that we can account for certain confounding factors that may have led to these results. Having said that, I think there's a tremendous excitement, there's tremendous excitement in this field. I gave you examples of, or highlighted, 3 studies: one in patients with EGFR exon 20 insertion mutations, another in KRAS G12C mutations, and the third in patients who may have already received either immunotherapy or chemoimmunotherapy. We will continue to update our Cancer.Net website with updates as they come through, new advances, new studies, so thanks for following, thanks for listening, and more to come. Stay tuned. Thank you. ASCO: Thank you, Dr. Aggarwal. Next, Dr. Christopher Flowers will discuss new research in treating people with different subtypes of lymphoma, including mantle cell lymphoma and diffuse large B-cell lymphoma. Dr. Flowers is the Chair of the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center and was appointed Division Head ad interim of Cancer Medicine in August 2020. He is also the 2022 Cancer.Net Associate Editor for Lymphoma.   You can view Dr. Flowers' disclosures at Cancer.Net. Dr. Flowers: Hello and welcome to this podcast that is a review of late breaking abstracts from the ASCO Meeting and recent updates in lymphoma. I'm Dr. Christopher Flowers, professor and chair of the Department of Lymphoma and Myeloma and Interim Division Head for Cancer Medicine at The University of Texas MD Anderson. And it's my great pleasure to discuss with you some of these late breaking abstracts. I do have some disclosures that are related to the content that I will present from this year's ASCO Meeting and recent studies in lymphomas. Those are available at Cancer.Net. Those relate to my role as a consultant for the development of clinical trials in lymphomas and research funding that MD Anderson has received from companies related to my role in clinical trials in lymphoma and clinical trials across cancers. So, the ASCO Meeting had a host of new information that was presented. Some of that information centers around key clinical trials. One that was a pivotal clinical trial, the SHINE clinical trial, looked at patients with mantle cell lymphoma, a rarer lymphoma subtype, that looked at the combination of bendamustine and rituximab, a standard chemoimmunotherapy combination, compared to that same chemoimmunotherapy combination, bendamustine, rituximab, plus the Bruton's tyrosine kinase inhibitor ibrutinib. Ibrutinib, as some of you may know, is a kind of therapy that is typically used in the relapse setting for patients with mantle cell lymphoma when they have their disease come back. And the SHINE clinical trial was looking at adding it to frontline therapy. What this randomized, controlled trial in the phase 3 setting found was that patients who received the combination of bendamustine, rituximab, plus ibrutinib had improvement in their progression-free survival, meaning that the time that it took for their disease to come back or them to have deaths related to the lymphoma was longer for patients who received this combination. About 2.3 years longer than the group that received bendamustine, rituximab, plus placebo. And in total, that led to a median progression-free survival of 6.7 years. That study has now been published in the New England Journal of Medicine and was led by my colleague Dr. Michael Wong from MD Anderson. Dr. Wong also led another study that was presented at the ASCO Meeting looking at CAR T-cell therapy for patients with mantle cell lymphoma. That study has now been published in the Journal of Clinical Oncology, and it looks at brexucabtagene autoleucel, a kind of CAR T-cell therapy, where that-- the CAR T-cell therapy was successfully manufactured for 71 of the 74 patients in the trial. 68 of those patients received an infusion and the median progression-free survival, so the average amount of time that it took for patients to have progression of their disease, was about 25 months. And so a marked benefit for those patients who were receiving CAR T-cell therapy when their mantle cell lymphoma came back. There also were major breaking abstracts at the ASCO Meeting in the area of diffuse large B-cell lymphoma. As many of you may know, diffuse large B-cell lymphoma is the most common type of lymphoma that occurs in the United States. And there was a breaking trial that was presented in December at the American Society of Hematology Meeting describing polatuzumab, a CD79b antibody drug conjugate, as a new drug in the substitution of frontline therapy for patients with diffuse large B-cell lymphoma in combinations with rituximab, cyclophosphamide, adriamycin, and prednisone, or the pola-R-CHP arm, that compared favorably to rituximab and CHOP chemotherapy, which has been the standard of care for patients with diffuse large B-cell lymphoma. And that trial showed an improvement in progression-free survival. At this year's ASCO Meeting, Franck Morschhauser presented results from looking at subsets of that patient population. Those patients who had BCL2 by immunohistochemistry that was positive or MYC expression by immunohistochemistry that was positive, or both of those, what we call double-expressor lymphomas, those who have poorer risk than standard groups. And those double-expressor lymphomas, treated with pola-R-CHP, had improvement in progression-free survival compared to R-CHOP with a hazard ratio of 0.64 in that group. We also saw in a multitude of analysis that that supported the benefit of pola-R-CHP in patients with both BCL2-positive and MYC-positive diffuse large B-cell lymphoma. Another area that has been very hot in diffuse large B-cell lymphoma clinical trials is the role of bispecific antibodies. Bispecific antibodies are antibodies that bind both to CD20, a marker on the diffuse large B-cell or the lymphoma cells, and to the marker CD3, which is a marker on T-cells which brings the normal T-cells of the immune system in close proximity to the lymphoma cells and then leads to immune-directed killing of lymphoma cells. The agent glofitamab is an agent that was presented by Michael Dickinson at this year's ASCO Meeting in an abstract. And in this study, 107 patients who received more than 1 dose of steady treatment went on to have complete responses in about 35% of patients. And this showed that glofitamab induced durable complete responses and had a very favorable safety profile in patients with relapsed and refractory diffuse large B-cell lymphoma. And in this trial, they compared that also for patients who had prior exposure to CAR T-cells and showed that responses were also good in those patients. Another set of studies has also looked at bispecific antibodies and a whole host of other areas with multitude of other agents. Another study that was presented at this year's ASCO Meeting explored the use of bispecific antibodies in the frontline setting in combination with the R-CHOP regimen that I just discussed. In that study, Lorenzo Falchi presented results of the subcutaneous bispecific antibody epcoritamab in combination with R-CHOP. This was a relatively small study of 33 patients that showed that the combination of epcoritamab plus R-CHOP was something that was safe and tolerable. There were no new treatment emergent adverse events that led to discontinuation of epcoritamab in the study. And there are some adverse events that are of special interest that we see with the bispecific antibodies, and those include the kind of immune-mediated adverse events that we can also see with CAR T-cells, like cytokine release syndrome, or CRS, or neurologic toxicities that we can see there that are also called ICANS. What we've seen in this trial, that about 42% of patients had some form of cytokine release syndrome, but that most severe form of cytokine release syndrome, those that were greater than grade 3 in severity, was only in 3% of patients. And likewise, the neurologic toxicities, or ICANS, that were grade 2 was in only 3% of patients. Relatively few patients completed all therapy by the time that this was presented. Only 10 patients had completed 6 cycles of therapy, but that showed an overall response rate that was quite high in that patient population. There were a whole host of other trials that were presented at this year's ASCO Meeting, and those portend improved kinds of outcomes on the horizon for patients with lymphomas across the spectrum. And I think it's an exciting time moving forward for clinical trials in lymphoma and hopefully, to see new therapies that emerge for the management of this disease. One of those new therapies that happened outside of the ASCO Meeting was the recent FDA approval of CAR T-cell therapy in the relapse setting for follicular lymphoma. And this was based on the ELARA clinical trial. And I think the future is quite bright for therapies and for patients with lymphomas broadly. ASCO: Thank you, Dr. Flowers. Finally, Dr. Daniel Mulrooney will discuss new research in childhood cancers, including a study comparing treatment options for Ewing sarcoma, and several studies on neuroblastoma. Dr. Mulrooney is an Associate Member in the Division of Cancer Survivorship at St. Jude Children's Research Hospital. He is also the Cancer.Net Associate Editor for Pediatric Cancers. You can view Dr. Mulrooney's disclosures at Cancer.Net. Dr. Mulrooney: My name is Dr. Dan Mulrooney from St. Jude Children's Research Hospital. I'm the Deputy Director of the After Completion of Therapy Clinic at St. Jude and primary care for survivors of pediatric solid tumors. The annual ASCO Meeting is typically quite busy and full of research presentations sharing knowledge and advances in cancer treatment and care. Today, I'd like to highlight some of the exciting presentations in pediatric cancer. Please note, I do not have any relationships to disclose related to any of these studies. At this year's meeting, one of the highlights was a European study in patients with relapsed or refractory Ewing sarcoma. Ewing sarcoma is a rare bone cancer that typically occurs in adolescents or young adults. While challenging to treat, it is difficult to cure in patients who have relapsed, and studies are needed to improve the care of these patients. Investigators from 13 European countries and Australia and New Zealand studied the most common relapsed therapies, which include irinotecan and temozolomide, gemcitabine and docetaxel, topotecan and cyclophosphamide, or high-dose ifosfamide. The study enrolled 451 patients between 2014 and 2021 and randomly assigned them to one of these four treatments. Based on response rates, the first 2 arms were dropped and the study was largely a comparison between topotecan cyclophosphamide and high-dose ifosfamide. The main outcome was event-free survival. Event-free survival is a common way in a clinical trial to see how well a treatment works. It measures the time from treatment that the patient remains free of complications, such as return or progression of the cancer. But investigators also looked at overall survival, toxicity, and quality of life. The 6-month event-free survival was better for high-dose ifosfamide at 47% compared to 37% for topotecan cyclophosphamide. The median overall survival was also better for high-dose ifosfamide compared to topotecan cyclophosphamide. The results were best for children younger than 14 years old versus those 14 or greater. Toxicities included fever and neutropenia, nausea, vomiting, and diarrhea. Patients receiving high-dose ifosfamide had more neurologic and kidney toxicities, which might be expected since ifosfamide is known to affect these organ systems, while only descriptive measurements of quality of life appeared higher for those children treated with high-dose ifosfamide compared to topotecan and cyclophosphamide. The strength of this trial is its large size, particularly for a rare cancer, and the fact that it randomized patients to the most commonly used treatment regimens for relapsed Ewing sarcoma. Importantly, data did not previously exist comparing these different treatments. While the results of this study are promising, clearly more needs to be done, and there was a lot of discussion at the ASCO Meeting about how to further improve survival in these patients. This study provides some information for doctors and patients, but importantly, provides data to advance future trials, which will concentrate on incorporating new targeted drugs with high-dose ifosfamide. This study is ongoing and is adding additional arms to continue to improve the outcomes for patients with relapsed or refractory Ewing sarcoma. In addition to this study in Ewing sarcoma, several studies investigating neuroblastoma were presented. Neuroblastoma is the most common extracranial solid tumor in children and for children with high-risk disease requires intensive and prolonged treatment, including chemotherapy, surgery, radiation therapy, and stem cell transplantation. Treatment for these patients has improved since the introduction of immunotherapy, particularly an antibody directed at a particular antigen named GD2 on the neuroblastoma cells. One study showed improvement in outcomes using this antibody for children with relapsed or refractory neuroblastoma, and another study demonstrated feasibility of using this antibody earlier in treatment, which was not previously known to be safe and tolerable. In what is called the BEACON study, investigators tested whether the antibody, called dinutuximab, would be effective when combined with chemotherapy for relapsed or refractory neuroblastoma. They enrolled 65 patients from 2019 to 2021 and randomized these patients to either chemotherapy alone or chemotherapy plus dinutuximab. The median age of these children was 4 years. The overall response rate, which means either a complete or partial response, was 18% for the chemotherapy-only arm but improved to nearly 35% for those treated with chemotherapy and dinutuximab. The progression-free survival was 27% for chemotherapy only and improved to 57% for those treated with chemotherapy and the antibody. There was no change in overall survival, though investigators think this may have been due to some patients who had progressive disease and crossed over to the antibody arm of the study. This presentation was followed by a study from the Children's Oncology Group, which investigated the feasibility of adding antibody treatment earlier in the treatment regimen for neuroblastoma. Prior studies had used antibody later in treatment when the tumor burden is thought to be lower. The endpoint of this study was tolerability measured by toxic deaths or unacceptable toxicities, such as adverse reactions to the medication. For example, sustained low blood pressure requiring a ventilator or breathing machine, or severe neuropathy. 42 high-risk neuroblastoma patients were enrolled from 8 different children's hospitals between 2019 and 2021. 41 of the 42 were able to complete the induction chemotherapy plus the antibody. There were no toxic deaths or unacceptable toxicities. Importantly, 85% were able to complete the next phase of treatment, called the consolidation phase, and 79% were able to complete the following phase after consolidation, called post-consolidation. One-year event-free survival was 83%, and 1-year overall survival was 95%. Now, it's important to know these are still early results, and the trial recently closed, and some of the patients have only completed therapy within the last year. Both of these studies add to the knowledge of chemoimmunotherapy for children with high-risk neuroblastoma. These studies provide a foundation for larger randomized trials that will further advance the care of these children. And finally, another study looked at race, ethnic, and socioeconomic disparities among children treated for high-risk neuroblastoma on Children's Oncology Group studies. There were no differences in event-free survival, but there were differences in overall survival based on ethnicity. The 5-year survival was lowest for Hispanic patients at 47%, 50% for non-Hispanic other ethnicities, which included Asian, Native American, Native Hawaiian, or Pacific Islanders, and 62% for non-Hispanic Black and non-Hispanic White children. Importantly, these investigators also studied household and neighborhood poverty. Overall, survival was lower for children living in poverty, though some of these differences went away when accounting for other factors, such as stage of disease or high-risk features. This study is important because it highlights the increasing need to collect data on clinical trials that may contribute to inequities in outcomes. While most studies collect data on the race and ethnicity of participants, other factors known as social determinants of health, such as income, neighborhood, education, access to health care, and insurance coverage, may also contribute to outcomes in pediatric cancer patients. Overall, the studies highlighted here and presented at this year's ASCO Annual Meeting focused on difficult-to-treat cancers, such as relapse or refractory disease, and they have laid the groundwork for future investigations to continue to improve survival rates for all children diagnosed with a malignancy through improved therapies and by addressing potential social barriers. Thank you for listening to this brief summary of the new research in pediatric oncology presented at the 2022 ASCO Annual Meeting. ASCO: Thank you, Dr. Mulrooney. You can find more research from recent scientific meetings at www.cancer.net. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care. And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

Featuring perspectives from Dr Charu Aggarwal, including the following topics: Adjuvant and Neoadjuvant Treatment of Non-Small Cell Lung Cancer (NSCLC) Introduction (0:00) Case: A man in his late 60s with Stage IIA squamous cell carcinoma of the lung who received neoadjuvant pembrolizumab and radiation therapy on a clinical trial — Matthew Gubens, MD, MS (7:01) Case: A woman in her early 60s with a 1.7-cm adenocarcinoma of the lung and a 1.5-cm small cell lung cancer — Mohamed K Mohamed, MD, PhD (14:02) Stage III Unresectable NSCLC  Case: A woman in her early 70s with Stage III adenocarcinoma of the lung — Mamta Choksi, MD (26:47) Metastatic NSCLC  Case: A woman in her mid-50s with adenocarcinoma of the lung and multiple brain metastases — William R Mitchell, MD (37:56) Case: A man in his mid-60s with adenocarcinoma of the lung (no actionable mutations, PD-L1 >50%) — Laurie Matt-Amaral, MD, MPH (43:49) Case: A man in his early 60s with metastatic squamous cell carcinoma of the lung and PD-L1 >50% — Rahul Gosain, MD (47:41) Case: A man in his mid-60s with metastatic adenocarcinoma of the lung (PD-L1 TPS 20%) — Neil Morganstein, MD (51:55) Case: A woman in her early 60s with extensive-stage SCLC — Julia Saylors, MD (58:21) CME information and select publications

Featuring a discussion on role of immunotherapy in the management of lung cancer with Dr Charu Aggarwal, moderated by Dr Neil Love.

The IASLC Targeted Therapies Meeting has historically been a very interactive, fast-paced meeting that highlights the latest and most innovative anticancer drugs, initially focused on targeted agents but in recent years, extending to immunotherapy. In this Lung Cancer Considered podcast hosts Dr. Narjust Duma and Dr. Stephen Liu lead a wide-ranging discussion of the meeting with three lung cancer experts who attended the meeting: Dr. Lecia Sequist is a thoracic medical oncologist at Massachusetts General Hospital, the Landry Family Professor of Medicine at Harvard Medical School, the Director of the Center for Innovation in Early Cancer Detection and a board member of the IASLC. Ivy Elkins was diagnosed with Stage IV lung cancer in Dec 2013 as a healthy 47-year-old, Ivy was found to have an EGFR mutation and has spent the years since her diagnosis educating herself and advocating for herself and those within the lung cancer community. Ivy is a patient advocate and co-founder of the EGFR Resisters Lung Cancer Patient Group. Dr. Charu Aggarwal is a thoracic medical oncologist at the Hospital of the University of Pennsylvania and the Leslye M. Heisler Associate Professor for Lung Cancer Excellence at the University of Pennsylvania.

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. In this podcast, experts will discuss targeted therapy for lung cancer, including 2 new treatments that target a specific type of mutation or change in the EGFR gene in some cancer cells, called an EGFR exon 20 insertion. They will explain how targeted therapy works to treat cancer, why this specific mutation is different from other, more common EGFR mutations, and what these 2 new treatments mean for people with this type of cancer. This podcast will be led by Dr. Charu Aggarwal, Dr. Xiuning Le, Dr. Vamsidhar Velcheti, and Marcia Horn. Dr. Charu Aggarwal is the Leslye Heisler Associate Professor of Medicine in the Hematology-Oncology Division at the University of Pennsylvania's Perelman School of Medicine in Philadelphia, Pennsylvania. She is also the Cancer.Net Associate Editor for Lung Cancer.  Dr. Xiuning Le is an assistant professor in the Department of Thoracic/Head and Neck Medical Oncology in the Division of Internal Medicine at the University of Texas MD Anderson Cancer Center in Houston, Texas.  She is also a Cancer.Net advisory panelist for lung cancer.  Dr. Vamsidhar Velcheti is the director of thoracic medical oncology at NYU Langone's Perlmutter Cancer Center in New York, New York, and is also a Cancer.Net advisory panelist for lung cancer. Marcia Horn is the President and CEO of the International Cancer Advocacy Network and the executive director of the Exon 20 Group in Phoenix, Arizona.  View full disclosures for Dr. Aggarwal, Dr. Le, Dr. Velcheti, and Ms. Horn at Cancer.Net. Dr. Charu Aggarwal: Hello and welcome to this Cancer.Net podcast on new research in lung cancer. I'm Dr. Charu Aggarwal from the University of Pennsylvania. I'm also the Cancer.Net Associate Editor for Lung Cancer. I'm here today with my colleagues from the Cancer.Net Lung Cancer Panel. First is Dr. Xiuning Le from the University of Texas MD Anderson Cancer Center. Hi, Dr. Le. Dr. Xiuning Le: Hi, everyone. This is Xiuning Le from MD Anderson. I'm happy to be here as one of the discussants. Dr. Aggarwal: Next is Dr. Vamsi Velcheti from the NYU Langone Perlmutter Cancer Center. Vamsi? Dr. Vamsidhar Velcheti: Hi, this is Vamsi Velcheti. I'm so glad to be here with you. Dr. Aggarwal: And our special guest today is Marcia Horn, the president and CEO of the International Cancer Advocacy Network and the executive director of the Exon 20 Group. Hi Marcia. Marcia Horn: Hi, everyone. Wonderful to be here. Dr. Aggarwal: So good to have you all. Before we begin, we should mention that Marcia has consulted with both Takeda Oncology and Janssen on survey research for the Exon 20 Group. You can view full disclosures for this podcast at Cancer.Net. Our podcast today is going to be about targeted therapy for non-small cell lung cancer, and specifically, 2 new treatments that target a specific type of mutation or change in the EGFR gene in some cancer cells. This mutation is called an EGFR exon 20 insertion. Dr. Velcheti, I'll start off with you. What is targeted therapy, and how does it work? Dr. Velcheti: So thank you, Charu. Lung cancer is a very complex biological disease. There are a lot of genes in the tumor cells that could be mutated, and understanding the type of genetic changes or mutations in the DNA of these tumor cells helps us really develop treatments that are very focused on that particular patient's cancer. Having a specific gene alteration could render tumors more susceptible or vulnerable to certain treatments, and these are what we call targeted therapies. And in lung cancer, these are especially important because there are a lot of drugs developed for patients with certain unique genomic aberrations, or changes in the DNA, and it's ushered in a whole wave of new treatments for patients with lung cancer, and it's really an exciting time for patients with lung cancer. Dr. Aggarwal: That's terrific. And I would like to focus on the mutation aspect a little bit more. Dr. Le, can you talk to us [about] whether all mutations found in lung cancer, can all of them be treated? Dr. Le: Like Dr. Velcheti was talking about, lung cancer is really a complex disease. And oftentimes in 1 lung cancer, we can detect more than 1, multiple mutations. Some of them function as driving the cell growth. Some of them function as a brake. We call that a tumor suppressor to release the cell from being suppressed. Clinically, we usually classify all the mutations that can be detected in the lung cancer into the 2 groups. One is called actionable. The other group is called not actionable. Actionable, meaning when we detect a mutation, we, as clinicians, can actually offer a specific targeted therapy to act on the mutation. Therefore, detection of the actionable mutation oftentimes translates to the patient potentially having the opportunity to get targeted therapy targeting that potential actionable driver oncogene. As of today, we're talking, the development of lung cancer treatment has been so advanced. We have 9 actionable genetic alterations that can be detected in non-small cell lung cancer. Even since 2 years ago, there are 4 new additions, so a total of 9 as of today, and EGFR exon 20 is one of the newest being approved in 2021, so really good news. Dr. Aggarwal: I know we've come a long way, and EGFR exon 20 insertions have been known for a long time. However, we've also known that they are not perhaps as sensitizing as the other EGFR mutations. Dr. Velcheti, could you shed some light on what is unique about these mutations in terms of testing as well as application of therapies? Dr. Velcheti: We have known about EGFR mutations in lung cancer for a very long time, and there have been quite effective treatments for EGFR activating mutation-positive lung cancer patients. However, not all mutations in the EGFR gene are the same. Depending on the location of the sequence change in the gene, they could have a different degree of response to EGFR inhibitors. So when we talk about EGFR exon 20, we're talking about a subset of these EGFR gene mutations which is in an area of the EGFR gene, a change in the sequence of the EGFR gene, that doesn't necessarily respond so well to the novel EGFR inhibitors that we have been using for a long time. So the clinical implications, and it's something to kind of think about and remember, is that the way we test for these mutations is very different. You could do comprehensive genomic profiling, or in some cases, there are some tests that actually test for a specific type of gene mutation. So it's something we call “hotspot panels.” Those are tests using certain techniques that actually only pick up certain EGFR genes, and they don't pick up all the gene mutations that happen in the EGFR gene. So it is very important to kind of keep that in mind because now we have drugs approved for exon 20 mutations. If you don't actually pick them up on a test, then obviously, we can't identify those patients for treatment with these exciting new treatments. And also, just as a quick plug, given that we have so many new drugs approved for different types of gene alterations in lung cancer, it is even more important now to focus on doing really good biomarker testing with comprehensive genomic profiling looking at a wide panel of genes, rather than focusing on certain kinds of gene mutations. So this is what we call comprehensive genomic profiling. That's absolutely critical in order to identify patients for the right treatment with targeted therapy. So it's extremely important to do that upfront so that we have patients kind of matched up to the right treatment. Dr. Le: I do also want to add with Dr. Velcheti in that I fully agree that exon 20 is oftentimes not on the hotspot PCR-based testing, so please use a comprehensive, what we call, next-generation sequencing base. I also want to say that also, exon 20 can be detected in liquid biopsy. So it's not you have to do the tissue biopsy if the patient has the opportunity to get liquid biopsy. As long as it's a good, comprehensive panel, it should also be able to detect that. Dr. Aggarwal: Absolutely, can never underemphasize the benefits and importance of comprehensive testing. Marcia, I'll turn to you. You lead a large group called the Exon 20 Group. How common is the EGFR exon 20 insertion-- how common is this mutation in people with lung cancer? Marcia Horn: It's not at all common. In fact, EGFR exon 20 insertion mutations in non-small cell lung cancer are exceedingly rare, a total of about 2% of all NSCLC and about 9 to 10% of all EGFR mutations. And it's an insertion mutation that hits, for the most part, never-smokers and members of Asian populations, although we at the Exon 20 Group have seen diagnoses in virtually every racial and ethnic group imaginable. The Exon 20 Group was established in 2017 as a special project of ICAN. It was founded by an EGFR exon 20 insertion patient, Kevin Hamlin, and his brother, Bob Hamlin, who's a senior lecturer at MIT. What we all wanted to do was get an international working group put together, and before we knew it, we had this huge global coalition of not only many hundreds of patients for EGFR exon 20 insertion and HER2 exon 20 insertion representing about 54 countries, but we had care partners, family members, several hundred leading thoracic oncologists, medical oncologists, and members of the community oncology setting as well, plus biotechs, pharmas with drugs in the exon 20 pipeline, and members from molecular profiling labs and the basic sciences in exon 20 bench science. So altogether, we're working to turn this into a chronic and manageable disease, and for the last 4 and a half years, we've been connecting our patients to promising clinical trials, especially the 2 newly approved drugs, and our angel buddy program provides our patients with peer-to-peer counseling to help them through side effects. So we're all united in blasting this disease off the planet and making the patient journey far more manageable. Dr. Aggarwal: Incredible. I'm just so proud of what all you've achieved, and you serve such an important mission in terms of patient advocacy and, more importantly, support. Dr. Velcheti, there have been 2 new recently approved targeted therapies to treat non-small cell lung cancer that harbors an EGFR exon 20 insertion mutation, and really, these drugs have come to us within the last few months. How does the first drug, mobocertinib, work to treat this cancer? Dr. Velcheti: Yeah, definitely. I think this is a really exciting time for thoracic oncology as we have more to offer our patients, especially for exon 20 and EGFR exon 20 specifically. We have 2 drugs now, FDA-approved, and mobocertinib is a small-molecule inhibitor. It's an oral drug, and this has been approved for patients who have EGFR exon 20 mutation. This is for patients who have already had platinum-based chemotherapy, and they have progressed, and these patients could now be treated with mobocertinib. Certainly, the activity, it seems like a very active drug. It's very promising. It's kind of similar to the other small-molecule targeted therapies that we have, but it does have side effects. Patients could potentially have diarrhea, which is kind of similar to other EGFR small-molecule inhibitors or drugs in the class, so it's something to kind of know when patients are being treated with this drug. Certainly, it's really nice to have more treatment options for these patients. So I think now we haven't had any EGFR small-molecule inhibitors show significant efficacy in this patient population, so this is a really welcome approval for patients. And there's also a new drug, which I'm sure Dr. Le is going to be talking about, amivantamab, which could also be an option for these patients. Dr. Aggarwal: Speaking of, let's turn to Dr. Le about amivantamab. Can you tell us a little bit more? Dr. Le: Yeah, amivantamab, again, represents a very exciting approval. I think, like Dr. Velcheti was talking about, the small-molecule inhibitor, but amivantamab represents a brand-new class of potential agents for exon 20 and many other oncogene targets in lung cancer. So amivantamab, as the name signifies, is an antibody drug. It's not an oral drug. It's an IV drug. The antibody has 2 heads, basically. One is targeting EGFR. The other is targeting another oncogene called MET. So it's a bispecific antibody. The mechanism of action is also different than the small-molecule inhibitor such as mobocertinib in that it's not disabling the ATP-binding kinase activity of EGFR, rather than its antibodies to go after the EGFR on the cell surface and disable or internalize the receptor a different way. So I say that we're excited because it represents a really brand-new group of targeted therapy that we're probably going to see coming in the next decade, not just limited to the small-molecule inhibitor, of course, from the research, and also opens opportunity for future combinations. In terms of usage, so again, this medication is approved in patients who have EGFR exon 20 insertion, who had prior treatment. It's an IV treatment, and then the IV is rather frequent, every 2 weeks. The drug showed really great safety and then induced response in about 40% of the patients, a nice addition to the tools we have that we can battle the disease. Dr. Aggarwal: It's amazing that we have 2 drugs in this space. Can you talk, in your personal experience, pros and cons of each approach and if there is any data to guide using 1 drug versus another or in sequence? We'll start with you, Dr. Le, and then we'll go to Dr. Velcheti. Dr. Le: Yeah. So that's a very good question. I don't think we have the 1 perfect answer because we haven't conducted either head-to-head trials or sequential trials. When I'm in my clinic, I tell my patients that both of them are valid options. And most likely, 1 patient will be receiving 1 and the other because I think each of the medications also have a limit of after a certain time, the disease will continue to progress. So we shouldn't be ruling out either of them rather than thinking of them as being the sequential treatment. One thing I do also discuss with the patient is the drug administration - one is IV; one is oral - and then toxicity profile. The amivantamab, the most common issue is the infusion reaction in the first time that the patient's receiving it. However, after that's properly managed, the drug is really easy to tolerate down the line. So usually, I present both options to patients. I would have to say that numerically speaking, the response rate of amivantamab is higher than the reported of mobocertinib. So sometimes, together with the patients and family, we decide to go for amivantamab first and then save oral TKI as the next option, but really, there's no right or wrong. And then I tell the patient most likely, they will be receiving both in the end. Dr. Aggarwal: Your thoughts, Dr. Velcheti, on that approach? Anything different that you do? Dr. Velcheti: No, I completely agree with Dr. Le. Both of them are very different drugs. So Dr. Le mentioned they work in very different ways. They have, most importantly, very different adverse event profile. So we don't know about what the right sequencing should be. We don't have those studies to really inform us. But I do the same thing that Dr. Le just mentioned. Given slightly higher response rates, we tend to use amivantamab first, but again, it's really patient preference. I've had patients who said they don't want to have IV infusions. They prefer oral treatment. They don't want to come into the hospital that often. And there are some patients who are really concerned about the diarrhea. So it's really hard to kind of know what would be the perfect sequence, and especially, it's a rare population, so it's going to be really hard to do a trial, to kind of do a cross-trial comparison. That's all we have here in terms of making decisions. The other thing to also consider is, do we use these 2 drugs, one after the other, if they progress? I think given that they work in a very different way mechanistically, I do think if you progress on mobocertinib that doesn't necessarily mean you will not respond to amivantamab and vice versa. So I would encourage trying sequential approach. And also the other thing to also keep in mind is there are a lot of clinical trials with exciting drugs which are in the pipeline, and, of course, some of the data has already been presented and those look really promising. So I highly encourage patients to kind of consider participating in clinical trials. Dr. Aggarwal: That's such a fantastic summary. And Marcia, I will turn to you. What do these new drugs mean for patients with this rare subset of an actionable mutation? Marcia Horn: I totally agree with Dr. Le and Dr. Velcheti and their comments based on their deep, deep experience with EGFR exon 20 insertion patients. No question that, from the point of view of the Exon 20 Group, we were totally thrilled at the FDA approvals of both amivantamab and mobocertinib. And we, like everyone else, affectionately call both drugs as ami and mobo. These drugs are providing a concrete lifeline of hope, for the first time, that patients' lives can be extended and patient journeys can be manageable in terms of side effects. So what we're really excited about in the Exon 20 Group is not only the continuing clinical development of ami and mobo and other promising drugs in the pipeline, as Dr. Velcheti said, but we're looking forward to seeing ami and mobo in combination with second drugs. We're awaiting data down the road, obviously, from the ongoing amivantamab plus lazertinib trial that is recruiting, in part, EGFR exon 20 insertion patients, and we're really excited about drugs that can be combined with mobocertinib as well. We want a robust pipeline of numerous choices and good compounds. Dr. Aggarwal: And Marcia, given the amount of information in this subgroup, what questions should patients ask their doctors about these new treatments? Marcia Horn: We really think it's important for patients on diagnosis to ask their clinicians what the method of communication is going to be between patient and physician. This is not only important on diagnosis of EGFR exon 20 insertion mutated cancer, but it's really, really important when the patient is accessing either ami or mobo or a drug in clinical trials. So patients need answers on who is going to be answering their questions about side effects when they write those questions into a patient portal, and they have to have the sense that somebody is going to be listening to them in the event that the collateral medications that an oncologist may be giving them in conjunction with a clinical trial drug or in tandem with either ami or mobo-- if those collateral medications are not tamping down on side effects to the extent that we all want to see, we, for sure, want that patient to be talking to the treatment team, the study team, or whoever, and getting some quick answers because frankly, nothing is more tragic than a patient withdrawing from a drug for failure to manage toxicities, and we never want to see that happen. We do everything possible at the Exon 20 Group to make sure patients are outfitted with angel buddies who have lived, battle-hardened experience with that particular drug, and these drugs are manageable. Dr. Aggarwal: So much excitement going on in this space, and we are thrilled to be able to offer these approaches. But I will just summarize that we wouldn't be able to extend these benefits if we don't test, and comprehensive testing remains critical in diagnosing and delivering appropriate therapy. Thank you so much, Dr. Le, Dr. Vamsi Velcheti, as well as Marcia, for joining us today for this Cancer.Net podcast. You can learn more about lung cancer and how it's treated by visiting Cancer.Net. Thank you, everyone. Dr. Le: Thank you. Marcia Horn: Thank you. ASCO: Thank you, Dr. Aggarwal, Dr. Le, Dr. Velcheti, and Ms. Horn. Learn more about lung cancer at www.cancer.net/lung. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts. This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

Dr. MJ Markham, Chief of Heme-Onc at Univ of Florida, chats with Drs. Charu Aggarwal and Jack West about the intersection of gynecologic & medical oncology, COVID-19 blogging, gender bias, and social media dissemination of new results in cancer care.

Dr. Aaron Goodman of UCSD speaks with hosts Jack West and Charu Aggarwal explaining the remarkable level of engagement he achieves in offering medical education on hematology via Twitter, especially his wildly successful polls.

Dr. Mikkael Sekeres of Univ of Miami chats with Charu Aggarwal and Jack West about challenges and opportunities with his move from Cleveland to Miami, his commitment to writing for a broad audience, & challenges for MDs & patients in the wake of COVID-19.

Caris Precision Oncology Alliance™ Chairman, Dr. Chadi Nabhan, sits down with Dr. Charu Aggarwal, the Leslye Heisler Associate Professor of Medicine in the Hematology-Oncology Division at the University of Pennsylvania Perelman School of Medicine. Together they discuss the latest findings and top abstracts in thoracic oncology that were presented at this year's ASCO meeting. For more information, please visit: www.CarisLifeSciences.com

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's episode, 3 Cancer.Net Associate Editors discuss new research in lung cancer, breast cancer, and sarcomas presented at the 2021 ASCO Annual Meeting, held virtually June 4-8. First, Dr. Charu Aggarwal discusses new research on targeted therapy and immunotherapy to treat non-small cell lung cancer. Dr. Aggarwal is a medical oncologist and Leslye M. Heisler Associate Professor for Lung Cancer in the Hematology-Oncology Division at the University of Pennsylvania's Perelman School of Medicine. She is also the Cancer.Net Associate Editor for Lung Cancer. View Dr. Aggarwal's disclosures at Cancer.Net. Dr. Charu Aggarwal: Hello, I'm Dr. Charu Aggarwal. I'm a thoracic medical oncologist, and I'm here to talk to you about research that was recently presented at the 2021 ASCO Annual Meeting. I will be discussing 3 studies of interest, and I should say that I do have a relevant disclosure to share. I have served as an adviser and consultant to AstraZeneca, which produces 1 of the compounds called durvalumab, for which I will be discussing research on. So let's start off with what was the most exciting or practice-changing research in thoracic oncology presented this year. We know that lung cancer as a field is changing quite fast and, in fact, is really becoming a poster child for application of targeted therapies. At this year's ASCO Annual Meeting, we heard about sotorasib, which is a first-in-class oral therapy that selectively and irreversibly targets the previously undruggable KRAS G12C mutant protein. KRAS G12C is an oncogene, or a molecular mutation, that occurs in patients with non-small cell lung cancer and accounts for about 13% of all patients with metastatic non-squamous non-small cell lung cancer. In a clinical trial called the CodeBreaK 100 phase 2 trial, patients with metastatic non-small cell lung cancer with this particular mutation in KRAS G12C were enrolled to receive sotorasib, which was administered orally at a dose of 960 milligrams once daily. Patients could have received previous chemotherapy or immunotherapy. And what we found was that out of the 124 patients that received therapy on this single-arm clinical trial, about 37.1% of the patients had objective clinical response, meaning that their tumors shrank when assessed by radiographic imaging. Patients on this clinical trial had a median overall survival of about 12 and a half months, and patients were [responding] noticeably, with a response as early as 6 weeks, which was the time of the first assessment. Overall, this drug is very well-tolerated and, in fact, welcome news that the FDA approved use of this therapy for second-line and beyond treatment of patients that harbor a KRAS G12C mutation. So this is immediately practice-changing, it applies to a lot of our patients, and I think will serve as a really nice, immediate next therapeutic option in the second-line setting for our patients. The next study that I want to talk about is the updated analysis of a trial called PACIFIC. We heard a 5-year update on this clinical trial at this year's annual ASCO meeting. For patients that have locally advanced non-small cell lung cancer, the current standard of care involves using combination chemotherapy and radiation, usually with a platinum-based chemotherapy for 6 to 7 weeks, followed by 1 year of immunotherapy with a drug called durvalumab. This standard of care has been based on a clinical trial called PACIFIC, which was first released in 2017, and then updated in 2018, showing a significant advantage to the use of this agent in the consolidation setting. At this year's meeting, we saw a 5-year update of the patients that were enrolled onto this large, phase 3 clinical trial. Patients were randomized to either receive 1 year of durvalumab or placebo following concurrent chemoradiation therapy for stage III non-small cell lung cancer. At 5 years, we saw a consistent advantage in overall survival compared to placebo for patients that received durvalumab for 1 year following their definitive chemoradiation therapy. While these results are not immediately practice-changing, these are absolutely practice-affirming because looking at these curves at the 5-year time point really enable us to deliver the confidence to our patients that administering this 1 year of immunotherapy will help and improve overall survival and really improving the chances of cure following treatment for locally advanced, metastatic non-small cell lung cancer. The last study that I would like to discuss is a study of adjuvant immunotherapy that is using immunotherapy after surgical resection for early-stage non-small cell lung cancer. While the study is not immediately practice-changing, I think this does represent a new paradigm. Currently, the standard of care in the post-surgical setting involves chemotherapy in case of involvement of lymph nodes and/or additional radiation therapy depending on which level of lymph nodes may be involved. This study, called the IMpower010 study, asked the question if immunotherapy in this setting following surgical resection and chemotherapy could provide a benefit. They looked at about 1,200 patients that were enrolled following surgical resection and had received 4 cycles of chemotherapy. Patients were then randomized to receive 1 year of immunotherapy with atezolizumab or best supportive care and were followed for survival. At this year's meeting, we heard that patients who received atezolizumab, especially those patients that had stage II or IIIA non-small cell lung cancer, had a reduced chance of recurrence. Following the use of 1 year of atezolizumab, the chances of reduction in recurrence were about 34%, indicating that this is a positive study. I should add that atezolizumab for this indication has not been currently approved. Therefore, it is not practice-changing. However, I should also add that this is the first study of its kind to show an improvement in recurrence outcomes with the use of immunotherapy in the early-stage non-small cell lung cancer setting, making it a very notable study for this subgroup of patients. Again, I think this has been a very exciting year for lung cancer research. And that wraps up our brief summary of new research in thoracic oncology from the 2021 ASCO Annual Meeting. Thank you for listening. ASCO: Next, Dr. Norah Lynn Henry discusses two studies looking at new treatment options for early-stage breast cancer. Dr. Henry is an Associate Professor in the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and is the Breast Oncology Disease Lead at the Rogel Cancer Center. She is also the Cancer.Net Associate Editor for Breast Cancer. View Dr. Henry's disclosures at Cancer.Net. Dr. Norah Lynn Henry: Hi, I'm Dr. Lynn Henry, a breast cancer oncologist from the University of Michigan Rogel Cancer Center. Welcome to this quick summary of updates in breast cancer from the 2021 Virtual ASCO Annual Meeting. I have no conflicts of interest for any of the trials that I will talk about. Today I'm going to focus primarily on treatment of non-metastatic breast cancer, especially that occurs in patients who have inherited mutations in BRCA1 or BRCA2. When these 2 genes have mutations or changes that decrease their function, it increases the risk of someone developing breast cancer as well as other cancers. But it also can give us clues as to which types of treatments these cancers may respond to. I'm also going to talk about a second study that was smaller, that looked at whether allowing patients to keep their ovarian function after chemotherapy is actually a safe thing to do. One of the biggest stories from at the ASCO Annual Meeting was the results of the OlympiA trial. So in this trial, researchers studied a type of medication known as a PARP inhibitor, which is known to be effective for treating patients with metastatic breast cancer who have inherited mutations in those 2 genes I mentioned, BRCA1 and BRCA2. However, it was not known whether giving PARP inhibitors to patients with non-metastatic breast cancer would actually decrease the likelihood of their cancer returning. Therefore, in the OlympiA trial, researchers tried to answer this question. The OlympiA trial enrolled almost 2,000 patients who had inherited mutations in either BRCA1 or BRCA2. These patients had been diagnosed with either estrogen-positive or negative breast cancer, but HER2-negative breast cancer and were at high risk of having their cancer return. In this trial, patients were randomized like the flip of a coin to treatment with either the PARP inhibitor called olaparib or to a placebo for 1 year. Patients took the study medication in addition to their usual treatments. They had mostly all had chemotherapy already, and they took it at the same time as their anti-hormone therapy. After following patients for 3 years, the researchers found that the patients who got olaparib had more than a 40% decrease in the likelihood of their cancer coming back compared to those who got the placebo. The medication was pretty well tolerated. There was some nausea and vomiting, fatigue, and lowered blood counts, although there were some rare but serious side effects that can occur. So there are some concerns about using the medicine in everybody. The follow-up of the patients has been fairly short so far, only 3 years. So it is not yet known whether taking this medicine will enable patients to live longer after breast cancer. This is a medication that has already been approved by the FDA for treatment of patients with metastatic disease. And based on these data from the OlympiA trial, ASCO guidelines now recommend that olaparib should be considered as part of treatment for patients who have either a BRCA1 or a BRCA2 mutation and who have early-stage breast cancer who are at high risk of having their breast cancer recurrence. So to switch gears a little bit, I'll talk about the other study I also found interesting. Often very young women who are diagnosed with breast cancer would like to become pregnant after they undergo treatment with chemotherapy. For these patients who want to become pregnant in the future, we often treat them with a medicine to block the function of their ovaries during chemo, sort of to put them to sleep with the hope that it will increase the likelihood that their ovaries will wake up and resume functioning again after chemotherapy is complete. However, we have worried that preserving the function of the ovaries might increase the risk of breast cancer returning, especially for women who have hormone receptor-positive breast cancer. This is because ovaries make estrogen, which is important for those types of cancers to survive. Investigators from Italy conducted a randomized study called PROMISE-GIM6 in which patients were treated either with standard chemotherapy or they got standard chemotherapy plus the ovary-blocking medicine. Now that they followed women on this study for more than 12 years after their diagnosis of breast cancer, they presented their final results. Importantly, they found there was no difference in the likelihood of cancer returning or in survival for patients who did or did not have their ovary function blocked during chemo. So these results should be very reassuring for patients who want to try to preserve their ovary function while they're getting treatment for their breast cancer. Now, there were a lot of other research findings presented that were related to treatment for breast cancer at the meeting. Importantly, we got glimpses of the many new drugs on the horizon for treatment of breast cancer. And we eagerly await the results of large, randomized trials so that the drugs that work can be used to care for patients with breast cancer. But for now, that's it for this quick summary of important research from the 2021 Virtual ASCO Annual Meeting. Overall, we continue on a fast track with breast cancer with many new and exciting therapies being actively studied, as well as research helping support our patients to do better than ever before. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. ASCO: Thank you Dr. Henry. Finally, Dr. Vicki Keedy discusses two studies in metastatic synovial sarcoma. Dr. Keedy is an Associate 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. Vicki Keedy: Hello, my name is Vicki Keedy, and I'm a medical oncologist at Vanderbilt University Medical Center, and I specialize in the treatment of patients with sarcomas. Today, I'm going to talk about 2 important studies discussed at the 2021 ASCO Annual Meeting. The first is the SPEARHEAD-1 trial, which is a phase 2 trial for patients with metastatic synovial sarcoma or myxoid/round cell liposarcoma. I'd like to note that my institution participated in and enrolled patients onto this trial, and I have participated as an advisor to this trial. The study evaluated an immunotherapy-based treatment called afami-cel, which targets the MAGE-A4 protein. This protein, also called an antigen, is commonly found in synovial sarcoma and myxoid/round cell liposarcoma cells. Afami-cel is called a T-cell receptor therapy, or a form of cellular immunotherapy. This therapy uses a patient's own immune cells called T cells and engineers them to be able to recognize and eliminate cells that express the MAGE-A4 protein. For this trial, patients could be between 16 and 75 years old but must have had 1 prior anthracycline, such as doxorubicin or ifosfamide-based chemotherapy. For this therapy to be effective, patients' cells must also have a specific group of markers called HLA-A02. HLA-A02 testing is performed on the patient's blood sample, while MAGE-A4 is tested on the patient's tumor tissue. Patients who are eligible for this treatment have their T cells collected through a blood draw called leukapheresis. Patients then receive a short course of chemotherapy, followed by infusion of the T cells. Patients receive no further chemotherapy unless the cancer were to progress. The majority of patients on this trial have synovial sarcoma. The results show that 39% of patients had a partial response, meaning a decrease in tumor size by more than a third, and 2 patients had a complete response. While the number of responses is exciting, what is most exciting about these data is that these responses seem to last a long time despite the patients not receiving any further treatment for their cancer. Common side effects occurred to the chemotherapy portion of the regimen and were similar to what we would expect for chemotherapy. However, 1 particular side effect of interest for cellular therapies is called cytokine release syndrome. This occurs when inflammation occurs in response to the T-cell infusion. Patients can experience fever and flu-like symptoms or more serious illness. In this trial, 59% of patients experienced cytokine release syndrome, but only 1 patient had a more serious or grade-3 reaction. Patients must be re-monitored closely in the days and weeks following their infusion and are often hospitalized for part of this monitoring. A downside to this technology is that it requires both the correct HLA typing as well as tumor MAGE-A4 expression. In this trial population, only about 1 out of 3 patients were potentially eligible based on these 2 requirements. Having said that, the results of this trial suggest that T-cell receptor therapy against MAGE-A4 expressing synovial sarcoma and myxoid/round cell liposarcomas is a very exciting advancement for patients who are eligible for this type of treatment. Currently, this treatment is only available within a clinical trial, as it is not yet FDA approved. Another important study reported this year were the results of catequentinib compared to dacarbazine in patients with metastatic synovial sarcoma. My institution also participated and enrolled patients on the study. Catequentinib is an oral therapy called a tyrosine kinase inhibitor. It blocks the signaling of multiple receptors that are responsible for tumor cell growth and invasion. Dacarbazine is a cytotoxic chemotherapy that is commonly used to treat patients with several types of sarcomas. To be eligible for this trial, patients must have had at least 1 prior anthracycline-containing regimen. Patients could've had a prior tyrosine kinase inhibitor, such as pazopanib, which is currently FDA approved for most sarcomas in the United States. This trial met its main endpoint of improving progression-free survival or, in other words, slowing down tumor growth, compared to dacarbazine. Although the improvement was relatively small, from 1.6 months with dacarbazine to 2.9 months with catequentinib, the data showed that there are a portion of patients who experience much longer benefit with nearly a quarter of patients still having stable disease at 1 year on the drug compared to 4% with dacarbazine. Side effects were as expected with this class of drugs, including diarrhea, fatigue, elevated liver enzymes, and high blood pressure. Catequentinib is not yet approved for use outside a clinical trial. And it is not known whether it is superior or equivalent to pazopanib, which is FDA approved for non-liposarcoma sarcomas. These are only 2 examples of the interesting and important research being done to improve the treatment of patients with sarcoma. And while both happened to include patients with synovial sarcoma, the class of cancers known as sarcoma are actually 50 to 100 different cancers. Although it will not be possible to have a trial for every sarcoma subtype, through collaboration and patient education, we're able to research the individual sarcomas as the distinct entities that they are. Thus, it is important for patients with a metastatic sarcoma to go to centers that have trials for their specific disease when available. With this approach, we'll see even more advancements in the future for patients with sarcoma. Thank you very much for your time, and I hope I have more exciting findings to discuss in 2022. ASCO: Thank you Dr. Keedy.   You can find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts. This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

Charu Aggarwal is a Chevening Scholar awarded by British Commonwealth, and comes with more than 20 years of digital, creative & media strategy experience on Fortune 500 brands like P&G, GSK, Samsung, FOX Network & Nokia in Global, APAC and MENA remits. In this week's episode of our D&AD Jury President Series, Charu Aggarwal (Head of the Media Jury) talks about the importance of diversity in the judging room. The rise of DEY, and shift in the media landscape towards long term behaviour change.

Hosts Jack West and Charu Aggarwal meet with Dr. Vince Miller to discuss the process of deciding to move from academia to industry, the evolution of molecular marker testing, and the potential for EQRx to break the impasse of escalating cancer drug costs.

Hosts Jack West and Charu Aggarwal discuss with Dr. Samyukta Mullangi of Memorial Sloan-Kettering the limitations of the current state-based medical licensing requirements and several potential paths to adapt to telemedicine & current practice needs.

Interview with Charu Aggarwal, MD, and Lova Sun, MD, authors of Association Between KRAS Variant Status and Outcomes With First-line Immune Checkpoint Inhibitor–Based Therapy in Patients With Advanced Non–Small-Cell Lung Cancer

Interview with Charu Aggarwal, MD, and Lova Sun, MD, authors of Association Between KRAS Variant Status and Outcomes With First-line Immune Checkpoint Inhibitor–Based Therapy in Patients With Advanced Non–Small-Cell Lung Cancer

Hosts Jack West and Charu Aggarwal speak with radiation oncology experts David Palma of the London Health Sciences Centre and Puneeth Iyengar of University of Texas-Southwestern about the functional definition and treatment of oligometastatic cancer.

On today's episode, meet Dr. Charu Aggarwal. Dr. Aggarwal is the Leslye Heisler Assistant Professor of Medicine in the Hematology-Oncology Division at the University of Pennsylvania's Perelman School of Medicine. She is an active member of the Abramson Cancer Center (ACC) where she serves as Physician Leader for the clinical research program for Airways Malignancies. Dr. Aggarwal specializes in the management of patients with lung and head and neck cancer, with a specific and clinical research focus on the development of novel immunotherapeutic approaches, and the discovery and application of biomarkers to guide therapy and monitor treatment. She serves as the local and national principle investigator for multiple clinical trials focusing on the development of “targeted” immunotherapeutic approaches including cellular therapy and CAR-T for solid tumors.

Co-hosts Charu Aggarwal and Jack West are joined by Dr. Toni Choueiri to discuss the role of twitter for education, mentorship and a platform for sharing credible information.

Co-hosts Charu Aggarwal and Jack West are joined by Dr. Don Dizon to discuss the role social media plays in oncology, clinical trial enrollment and branding.

Co-hosts Charu Aggarwal and Jack West are joined by Dr. Jamie Von Roenn and Christopher Merlan to discuss the landscape of virtual meetings, digital engagements and future of oncology meetings beyond the pandemic.

Co-hosts Charu Aggarwal and Jack West are joined by guest expert Sanjay Popat to discuss how practice should change & open questions on molecular testing & adjuvant EGFR inhibitor osimertinib for resected early stage EGFR mutation-positive NSCLC.

Drs. Charu Aggarwal and Jack West host Dr. Mark Lewis of Intermountain Healthcare to explore different styles of how physicians use social media for education, connection in building community, and determining boundaries in what to share with #MedTwitter.