Podcasts about l858r

Dr. Jyoti Patel is back on the podcast to discuss the updates to the living guideline on therapy for stage IV NSCLC with driver alterations. She shares updated recommendations in the first- and second-line settings for patients with stage IV NSCLC and classical EGFR mutations, and the impact of these updates for clinicians and patients. We also look to the future to discuss ongoing developments in the field. Read the full living guideline update “Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.3” at www.asco.org/living-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/living-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-24-02785     Brittany Harvey: Welcome to the ASCO Guidelines Podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows including this one at asco.org/podcasts.   My name is Brittany Harvey and today I'm interviewing Dr. Jyoti Patel from Northwestern University, co-chair on “Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.3.” It's great to have you back on the show today, Dr. Patel. Dr. Jyoti Patel: Thanks so much. Happy to be here. Brittany Harvey: And then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Patel, who has joined us here today, are available online with the publication of the guideline and in the Journal of Clinical Oncology, which is linked in the show notes. So then, to dive into the content of this update, Dr. Patel, this clinical practice guideline for systemic therapy for patients with stage IV non small cell lung cancer with driver alterations is living, meaning that it's continuously reviewed and updated. So what data prompted this latest change to the recommendations? Dr. Jyoti Patel: Thanks so much. So it's really been an exciting time in the treatment of EGFR lung cancer, particularly this past year has required us to rethink approaches to front- and second-line therapy. In this particular update, we examined what patients in the front-line setting may be offered by their clinicians. And so we're talking about the population of classical EGFR mutations, so exon 19 and exon 21 L858R substitution. And so certainly for this population, osimertinib has a high level of evidence and should be offered to all patients at the time of diagnosis when they present with advanced disease. Our last update included a recommendation that patients could also get platinum doublet chemotherapy with osimertinib or osimertinib alone. This current recommendation also introduces another alternative therapy and that's the combination of amivantamab plus lazertinib. And so now, clinicians are faced with three really good options for their patients with EGFR exon19 deletion or L858R. Brittany Harvey: It's great to hear that there's this advance in the space, particularly for patients with these classical EGFR mutations that you mentioned. So what should clinicians know as they implement these new first-line recommendations? Dr. Jyoti Patel:  I think it's become more complex than ever. Certainly, we know again that patients should get osimertinib in the frontline setting. But we've been kind of stuck at progression-free survival that's between a year and a half and two years. And so we've really been looking at opportunities to intensify therapy. So one could certainly be with chemotherapy or switching over to amivantamab, the bispecific antibody that targets EGFR and MET plus lazertinib, an oral TKI that's very similar in structure to osimertinib. And when you're talking to a patient, it's really a conversation about balancing efficacy with toxicity. Unfortunately, as we know, there aren't that many free lunches. And so if we think about what a patient is hoping for in their therapy and how we can further personalize treatment options, really is important to look at some of the analyses for this study. So in the study of amivantamab plus lazertinib, we know that there were increased toxicities with a combination of both therapies. In fact, up to 75% of patients had over grade 3 toxicities, versus about 43% of patients with osimertinib monotherapy. And we know if we look back at FLAURA2, almost two thirds of patients with osimertinib and chemotherapy had grade 3 toxicities, compared to 27% of patients with osimertinib alone. So we certainly see an increase in toxicities. Then we have to ask ourselves, are those paper toxicities or ones that really impact patients? And we know that amivantamab, for example, causes significant cutaneous toxicities. With both of these therapies, whether it's chemotherapy or adding amivantamab, there's the burden of infusional visits and increased time in the doctor's office. Certainly with chemotherapy, there can be an increased incidence of myelosuppression. And so when we're thinking about advising our patients, certainly we need to talk about the toxicities. But one thing that we've been able to do is to look at the patients that were included in this trial. And what we really find is that in higher risk cohorts, particularly those that we know historically have done less well with standard osimertinib, so patients, for example, with CNS metastasis, for those patients with co-mutations, it may be that that additive benefit is significant. And so one example I think would be from the MARIPOSA study, again, the study of amivantamab and lazertinib versus chemotherapy. What we can say is that patients who had co-mutations, so patients with EGFR mutations as well as TP53, lazertinib and amivantamab led to a hazard ratio of 0.65 compared to osimertinib alone. So that was 18.2 months versus 12.9 months. And so this may be really important to patients. And we also see conversely that patients with wild type TP53, so those patients who didn't have the mutation, probably had equivalent survival regardless of therapy. So certainly, we need to prospectively study some of these high-risk cohorts. We've only seen progression-free survival in these studies. And so at this juncture, we can advise our patients about toxicity, the improvements in certain categories of progression-free survival, but we really still don't know how this pans out in overall survival. In many of these studies, all patients do not necessarily cross over to the study arm and so they may have lost the benefit of subsequent therapy. Brittany Harvey: Absolutely. It's very important to talk about that balance of benefits and risks and particularly those toxicities that you discussed. So I appreciate reviewing that recommendation and the considerations for clinicians for first-line therapy. This update also included a second-line treatment update. What is that update for patients with EGFR alterations? Dr. Jyoti Patel: So this is where it gets super tricky because we have a frontline option with amivantamab and now we've had an update in the second line option. So what we said is that for patients who have progressed on an EGFR TKI, and in the United States, certainly that's predominantly osimertinib, or those in other parts of the world that may have gotten an earlier generation TKI, but do not have evidence of T790M or other targetable mutations, we can offer patients chemotherapy with or without amivantamab. And so certainly we have seen that this again leads to improved survival. There have also been a number of studies looking at incorporation of PD-L1 and anti-VEGF therapies. And what we can say, I think pretty clearly is that multiple phase 3 trials have really shown no benefit of the addition of PD-1 to platinum chemotherapy. But there are some emerging bispecific antibodies that may target PD-1 as well as VEGF, or combinations of antibodies that target both of those pathways that may improve outcome. At this juncture, I think we feel that the evidence surrounding chemotherapy plus amivantamab is strongest, but there is certainly work in this space that will be of interest. Now, what happens if your patient received amivantamab and lazertinib in the frontline setting and then has progression? And so we're trying to understand resistance mechanisms and opportunities for treatment. What the panel decided to recommend, based on the available evidence, was that certainly those patients should get platinum-based chemotherapy, but there may also be a role for antivascular endothelial growth factor targeting therapy such as bevacizumab in patients in whom it would be safe. Brittany Harvey: Great. I appreciate you detailing those recommendations when it gets complicated in the second-line setting. So what should clinicians know as they implement these second-line recommendations too? Dr. Jyoti Patel: So certainly the frontline setting matters significantly. So if a patient gets osimertinib in the frontline setting, we generally suggest that patients undergo repeat testing to see if they have another targetable mutation. If they don't, then I think preferred therapy would be chemotherapy with or without amivantamab. And amivantamab leads to a significant improvement in progression-free survival and response rate at the cost of increased risk of toxicity. For patients who get FLAURA2 in the frontline setting, chemotherapy plus osimertinib, it's a little bit of an unclear space. Those patients most likely would get docetaxel with or without ramucirumab. But there are other agents that we hope to have available to our patients in the near future. For patients who receive amivantamab and osimertinib, we recommend that those patients get chemotherapy probably with anti-VEGF as demonstrated by multiple trials that have shown the improved progression-free survival with introduction of an anti-VEGF agent. And we've seen evidence of amivantamab in the third line setting, so it is likely that this question about sequencing really takes center stage in our next set of trials. When you're talking to a patient, I think again, it's absolutely important to discuss: What are their goals? How symptomatic or how fast is their progression? Are there ways in which patients may benefit from spot treatment oligoprogression such as radiation? When is the right time for introduction of amivantamab and when do we think patients need chemotherapy? Is it up front or predominantly in the second-line setting? Brittany Harvey: Definitely. And then you've just touched on the goals of treatment for individual patients. So in your view, what does this update mean for patients with stage IV non-small cell lung cancer and an EGFR alteration? Dr. Jyoti Patel: For patients, this is a time in which shared decision making really needs to take center stage. So our best patients are those patients that are best informed not only about their disease but also have a good understanding about what is important to them and their families in terms of care. And so bringing that shared understanding to the table again helps us think about this particular cancer as more of a journey rather than just a one off treatment. Therapy will hopefully be prolonged, and so it's absolutely important that we address toxicities, make therapies more tolerable, again, with the shared goal of living long and living well. Brittany Harvey: Absolutely. Those are key points to making sure that patients are living both longer and have a good quality of life during that time as well. So then, before you mentioned the possibility of future sequencing trials and other ongoing developments. What additional studies or future directions is the panel examining for future updates to this living guideline? Dr. Jyoti Patel: So certainly we're thinking about trials that look at, for example, cfDNA clearance. So are there patients that do well and can we detect that early on without having to intensify therapy on day 1 so it may be that we add chemotherapy a little bit later. I think really exciting are some of the new bispecific. The HARMONi-A trial was a trial in China of a novel bispecific, ivonescimab. And this drug targets both PD-1 and VEGF and it was combined with chemotherapy. And this trial found almost a doubling of progression-free survival with this drug in combination chemotherapy in an EGFR patient population. That study is being planned and being run in the United States to see if we have similar outcomes with a more diverse population. So certainly that's exciting. There are a number of antibody drug conjugates that are being studied in the post-chemotherapy setting as well. And I think we'll likely soon see a better understanding of what co-mutations and burden of disease really mean when we're thinking about assigning treatment. So which patients, again, need intensification of therapy and which patients may do really well on just an oral agent that they're taking at home with more tolerable toxicity than dual treatment. Brittany Harvey: Yes, we'll look forward to continued developments in these fields and seeing some of those studies come to fruition. So with that, I want to thank you for your work to rapidly and continuously update this guideline, and thank you for your time today, Dr. Patel. Dr. Jyoti Patel: Thanks so much, Brittany. It's really an exciting time for lung cancer and we hope that these updates really help physicians decide the best treatments for their patients. Again, it's a rapidly evolving landscape which is fantastic, but it does become more cumbersome to stay ahead of the literature. Brittany Harvey: Definitely. And so we appreciate your time and the panel's time spent reviewing this literature and providing this much needed information to clinicians everywhere. So finally, thank you to all of our listeners for tuning into the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/living-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the  Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.   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.  

Dr. Lyudmila Bazheova share the latest updates to the ASCO living guideline on therapy for stage IV non-small cell lung cancer with driver alterations. She discusses changes for patients with EGFR driver alterations in both the first- and second-line setting, and reviews the evidence supporting these updated recommendations, from trials such as MARIPOSA, MARIPOSA-2, CheckMate 722, and KEYNOTE-789. Stay tuned for future updates to this continuously updated guideline. Read the full update, “Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.2.” at www.asco.org/living-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/living-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-24-02133   Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows, including this one at asco.org/podcasts.   My name is Brittany Harvey and today I'm interviewing Dr. Lyudmila Bazhenova from University of California San Diego Moores Cancer Center, lead author on “Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.2.” Thank you for being here, Dr. Bazhenova. Dr. Lyudmila Bazhenova: It is my pleasure. Brittany Harvey: Then, before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Bazhenova, who has joined us on this episode today, are available online with the publication of the guideline update in the Journal of Clinical Oncology, which is linked in the show notes. So then, to kick us off on the content here, Dr. Bazhenova, this living clinical practice guideline for systemic therapy for patients with stage IV non-small cell lung cancer with driver alterations is being updated routinely as a living guideline. So what prompted the update to the recommendations in this latest version? Dr. Lyudmila Bazhenova: Living ASCO Guidelines are developed to keep up with rapidly changing evidence which affect treatment of our patients with lung cancer. In this recently published guideline, we reviewed new evidence for patients with metastatic lung cancer harboring driver alterations. We reviewed evidence from four published studies, MARIPOSA, MARIPOSA-2, CheckMate 722 and KEYNOTE-789 that resulted in updated guidelines. Brittany Harvey: Great. And then based off those four trials that you just mentioned, what are the updated recommendations for patients with stage IV non-small cell lung cancer and an EGFR exon 19 deletion or exon 21 L858R substitution? Dr. Lyudmila Bazhenova: In the previous guideline, we detailed FLAURA 2 study which was presented and published in the past. In this guideline, we specifically highlighted a phase 3 MARIPOSA trial which took patients with untreated advanced non-small cell lung cancer which harbored classical EGFR mutations such as EGFR deletion 19 and L858R. In this study, patients were randomly assigned to receive amivantamab plus lazertinib or osimertinib or lazertinib alone. And the study showed that the primary endpoint which was progression-free survival was longer with amivantamab plus lazertinib compared to osimertinib, and numerically the progression free survival was 23.7 months with ami-lazertinib versus 16.6 months with osimertinib which was statistically significant. The challenge that we have to face when discussing that option with our patients is increased toxicity with amivantamab and lazertinib combination. For example grade 3 treatment adverse events were 75% with amivantamab and lazertinib and 43% with osimertinib. So this will require shared decision making between our patients and ourselves. We also noticed in the guidelines that there was a subgroup analysis of that study showing that the patients with a higher disease burden, central nervous metastasis or brain metastasis as well as disease which considered to be a higher risk such as commutation, for example, p53 and liver metastasis, they might benefit from intensified therapy. However, another thing that we are highlighting in the guideline is that at this point we do not know how the intensification of therapy will change overall survival of our patients. So one needs to take into account increased toxicity with that combination. Brittany Harvey: So then Dr. Bazhenova, in addition to those updates for first line therapy, what are the updated recommendations for second line therapy? Dr. Lyudmila Bazhenova: For patients who have progressive disease on osimertinib or other EGFR tyrosine kinase inhibitors, we also updated our guidelines highlighting MARIPOSA 2 study. In the MARIPOSA 2 study, patients were assigned to chemotherapy versus amivantamab plus lazertinib plus chemotherapy versus amivantamab plus chemotherapy. And both of the amivantamab arms showed superiority in progression-free survival compared to chemotherapy alone arm and therefore this becomes an additional treatment option for our patients who develop resistance to osimertinib. In addition, we also updated the results which highlight the lack of efficacy of immunotherapy in the patients who progressed on osimertinib. There were two studies that we highlighted. One of them was a CheckMate 722 which randomly assigned patients with metastatic non-small cell lung cancer whose cancer has progressed on EGFR tyrosine kinase inhibitor to receive either chemotherapy or chemotherapy plus nivolumab which is an immune checkpoint inhibitor. And the second study was KEYNOTE-789 which had a very similar study design. Again, patients who progressed on EGFR TKI also were assigned to receive chemotherapy plus pembrolizumab or chemotherapy alone and in both of those studies there was no improvement in progression-free survival when adding immunotherapy to chemotherapy. So for all your patients who are progressing on EGFR tyrosine kinase inhibitors and you're thinking if additional immunotherapy is necessary, we now have two randomized phase 3 studies telling us that immunotherapy should not be used in addition to chemotherapy for patients who develop progression on osimertinib. Brittany Harvey: Understood. I appreciate you talking about the evidence that supports these latest recommendations from the expert panel. So then you've already touched on this a little bit in mentioning shared decision making and discussing toxicity with these new therapies, but what should clinicians know as they implement these new recommendations and how do these new recommendations fit into the previous recommendations made by the panel? Dr. Lyudmila Bazhenova: Our previous recommendations did not include a MARIPOSA trial, so did not include amivantamab and lazertinib. So in our current guidelines for patients with newly diagnosed treatment-naive EGFR classical mutations, we have three options. Number one is osimertinib, number two is osimertinib plus chemotherapy based on the FLAURA study that we highlighted in the prior version of the guidelines. And the third is amivantamab plus lazertinib. At this point, we do not have any randomized head-to-head studies of those combinations with an exception of FLAURA 2 which is osimertinib plus chemo versus osimertinib. And so the decisions will have to be made on a cross-trial comparison, taking into account patient wishes if they would like to receive chemotherapy or amivantamab plus lazertinib, understanding that this combination will result in increased toxicity. Brittany Harvey: Absolutely. I appreciate you detailing those considerations. So then finally, what do these new options mean for patients with non-small cell lung cancer and an EGFR alteration? Dr. Lyudmila Bazhenova: As a patient, it is important to also be aware of what options we have and have a direct dialogue with the physician, with the treating physician, trying to understand what option will fit with each individual patient's goals, life goals, as well as toxicity concerns. Brittany Harvey: Definitely. It's always great to have more options for patients and it's also important to discuss all of those options with their clinician as well. So I want to thank you so much for your work on this update and thank you for your time today, Dr. Bazhenova. Dr. Lyudmila Bazhenova: My pleasure. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/living-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app which is available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.   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.      

Description: On August 19th, the Food and Drug Administration approved lazertinib in combination with amivantamab for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations. In this episode of Lung Cancer Considered, host Dr. Narjust Florez talks with Dr. Julia Rotow about this therapy and the MARIPOSA trial, which evaluated the use of lazertinib in combination with amivantamab.. Guest: Dr. Julia Rotow, Clinical Director of the thoracic oncology group at Dana-Faber Cancer Institute, Assistant Professor of Medicine at Harvard Medical School.

Dr. Megan Daly presents the latest rapid recommendation update to the ASCO management of stage III NSCLC guideline, based on data from the phase III randomized LAURA trial, presented at the 2024 ASCO Annual Meeting, and subsequently published. She discusses the results of the trial, shares the updated recommendation from the expert panel, and the impact for both clinicians and patients. We also discuss future research in the area and exciting new developments to watch out for in the field. Read the full rapid update, “Management of Stage III Non-Small Cell Lung Cancer: ASCO Rapid Guideline Update” at www.asco.org/thoracic-cancer-guidelines. TRANSCRIPT   This guideline, clinical tools, and resources are available at www.asco.org/thoracic-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-24-01324. Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Megan Daly from the University of California Davis Comprehensive Cancer Center, lead author on, “Management of Stage III Non–Small-Cell Lung Cancer: ASCO Rapid Guideline Update.” Thank you for being here today, Dr. Daly. Dr. Megan Daly: Thanks for having me, Brittany. Brittany Harvey: Great. Then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Daly, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then, to start us off on the content of this update, first, this guideline was updated based off new evidence presented at the 2024 ASCO Annual Meeting. Dr. Daly, could you describe the trial that prompted this rapid update to the management of stage III non-small cell lung cancer guideline? Dr. Megan Daly: The trial that prompted this update is the LAURA trial. The LAURA trial was a phase III randomized trial conducted in patients with unresectable stage III non-small cell lung cancer harboring EGFR mutations, either exon 19 deletions or L858R insertions. Patients in this trial were randomized 2:1 between the third generation EGFR tyrosine kinase inhibitor osimertinib or placebo, and osimertinib or placebo were continued until progression or other reasons for discontinuation. Osimertinib was found to provide a considerable benefit in progression free survival, with a hazard ratio of 0.16. The median progression free survival for patients randomized to osimertinib was 39.1 months, and for patients on the placebo arm, it was 5.6 months. We did not yet have overall survival data from the LAURA trial. The data is not mature, but the considerable progression free survival benefit noted with osimertinib has drawn a lot of interest to this trial. Brittany Harvey: Absolutely. Thank you for describing the results of those trials and the endpoints. So then, based on this new evidence, what is the updated recommendation from the guideline expert panel? Dr. Megan Daly: The updated recommendation from the panel is that patients with unresectable stage III non-small cell lung cancer with an EGFR exon 19 deletion or exon 21 L858R mutation may be offered consolidation osimertinib after definitive chemoradiotherapy, which can be either platinum-based chemotherapy and thoracic radiation given either concurrently or sequentially. Our evidence quality is moderate and the strength of the recommendation is strong. Brittany Harvey: Great. And thank you for reviewing both the strength of the recommendation there as well as the evidence quality rating. So it's great to have this new option for patients. So what should clinicians know as they implement this new recommendation? Dr. Megan Daly: I think it's important for clinicians to know when they're counseling patients about considering osimertinib to understand that first, the LAURA trial enrolled patients who had common EGFR mutations. So exon 19 deletions or L858R mutations. Patients with other uncommon EGFR mutations were not included in the trial. It's important to know that overall survival data is not yet mature. We do not know yet whether the use of consolidation osimertinib leads to a survival benefit at this time. We only know that it leads to a progression-free survival benefit as compared to placebo. I think it's also important to know that there was increased toxicity noted on the experimental arm. Grade 3 or higher adverse events was significantly higher with the use of osimertinib. So these are all important considerations when counseling patients and considering the use of osimertinib. Brittany Harvey: Absolutely. Those are definitely key points, as you mentioned, to consider. And you've already touched on this a little bit. But how does this change impact patients living with stage III non-small cell lung cancer? Dr. Megan Daly: We do see in the LAURA trial a rather remarkable benefit for progression-free survival. The progression-free survival, as I already mentioned, increased from 5.6 months median on the control arm to 39.1 months on the experimental arm with consolidation osimertinib. So this is an exciting new option for patients with unresectable stage III non-small cell lung cancer who have one of these mutations to extend their progression-free survival by almost three years. And we hope that this progression-free survival benefit will end up translating into a considerable overall survival benefit as well. So, certainly, the overall survival data is eagerly awaited. Brittany Harvey: Definitely, this is a promising option for patients, and we look forward to future readouts of long-term data on this trial. So that's one of the outstanding questions here. But what other outstanding questions are there regarding the management of stage III non-small cell lung cancer? Dr. Megan Daly: I think what many of us question when we look at this data is whether we could extrapolate to the use of other targeted agents with other less common oncogenic driver mutations. Unfortunately, the answer is we simply don't know yet. We hope to see some ongoing data in the resectable setting. Doing randomized trials with rare oncogenic drivers in unresectable stage III lung cancer is very difficult, unfortunately, and there's always a degree of extrapolation for clinicians when trying to figure out how to best manage our patients. But for me, that's one of the biggest outstanding questions I think specifically ties into interpreting the LAURA trial and other related trials in patients with oncogenic driver mutations. I think there's still many outstanding questions about how we continue to improve outcomes for our patients with unresectable stage III non-small cell lung cancer, questions about how we optimize our radiation regimens to have the best possible local control while reducing toxicity. We still need to continue to have randomized trials looking at questions on optimizing radiation, optimizing concurrent chemotherapy, whether there are any settings where we might be able to reduce or omit chemotherapy in place of some of these newer agents. These are all outstanding questions that hopefully will be answered over the next several years. We also continue to have open questions about when patients are more appropriate for surgery and more appropriate for non-surgical options, those borderline patients with N2 nodes who may technically be surgical candidates or could potentially be downstaged with neoadjuvant therapy. So, I think there's a lot of exciting work going on in stage III right now. Brittany Harvey: Absolutely. We'll look forward to that more data that you mentioned for more optimal individualized options for these patients with stage III non-small cell lung cancer. And I want to thank you so much for your time to rapidly update this guideline based off new evidence presented and then published. And thank you for your time today, Dr. Daly. Dr. Megan Daly: Thank you, Brittany. It's great to be on here. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline update, go to www.asco.org/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.   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.      

Drs. Vamsi Velcheti and Nathan Pennell discuss novel approaches and key studies in lung cancer that were showcased at the 2024 ASCO Annual Meeting, including the Plenary abstracts LAURA and ADRIATIC.   TRANSCRIPT Dr. Vamsi Velcheti: Hello, I am Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast today. I'm a professor of medicine and director of thoracic medical oncology at the Perlmutter Cancer Center at NYU Langone Health. Today, I'm joined by Dr. Nate Pennell, the co-director of the Cleveland Clinic Lung Cancer Program and the vice chair of clinical research at the Taussig Cancer Center in Cleveland Clinic. Dr. Pennell is also the editor-in-chief of the ASCO Educational Book. Today, we will be discussing practice-changing abstracts and the exciting advances in lung cancer that were featured at the ASCO 2024 Annual Meeting. You'll find our full disclosures in the transcript of the episode. Nate, we're delighted to have you back on the podcast today. Thanks for being here. It was an exciting Annual Meeting with a lot of important updates in lung cancer. Dr. Nate Pennell: Thanks, Vamsi. I'm glad to be back. And yes, it was a huge year for lung. So I'm glad that we got a chance to discuss all of these late-breaking abstracts that we didn't get to talk about during the prelim podcast. Dr. Vamsi Velcheti: Let's dive in. Nate, it was wonderful to see all the exciting data, and one of the abstracts in the Plenary Session caught my attention, LBA3. In this study, the investigators did a comparative large-scale effectiveness trial of early palliative care delivered via telehealth versus in-person among patients with advanced non-small cell lung cancer. And the study is very promising. Could you tell us a little bit more about the study and your take-home messages? Dr. Nate Pennell: Yes, I think this was a very important study. So just to put things in perspective, it's now been more than a decade since Dr. Jennifer Temel and her group at Massachusetts General Hospital did a randomized study that showed that early interventions with palliative medicine consultation in patients with advanced non-small cell lung cancer significantly improves quality of life and in her initial study, perhaps even overall survival. And since then, there have been numerous studies that have basically reproduced this effect, showing that getting palliative medicine involved in people with advanced cancer, multiple different cancer types, really, has benefits.  The difficulty in applying this has been that palliative care-trained specialists are few and far between, and many people simply don't have easy access to palliative medicine-trained physicians and providers. So with that in mind, Dr. Temel and her group designed a randomized study called the REACH PC trial, where 1,250 patients were randomized with advanced non-small cell lung cancer to either in-person palliative medicine visits which is sort of the standard, or one in-person assessment followed by monthly telemedicine video visits with palliative medicine. Primary endpoint was essentially to show that it was equivalent in terms of quality of life and patient satisfaction. And what was exciting about this was that it absolutely was. I mean, pretty much across the board in all the metrics that were measured, the quality-of-life, the patient satisfaction, the anxiety and depression scores, all were equivalent between doing telemedicine visits and in-person visits. And this hopefully will now extend the ability to get this kind of benefit to a much larger group of people who don't have to geographically be located near a palliative medicine program. Dr. Vamsi Velcheti: Yeah, I think it's a great abstract, Nate and I actually was very impressed by the ASCO committee for selecting this for the Plenary. We typically don't see supportive care studies highlighted in such a way at ASCO. This really highlights the need for true interdisciplinary care for our patients. And as you said, this study will clearly address that unmet need in terms of providing access to palliative care for a lot of patients who otherwise wouldn't have access. I'm really glad to see those results. Dr. Nate Pennell: It was. And that really went along with Dr. Schuchter's theme this year of bringing care to patients incorporating supportive care. So I agree with you.  Now, moving to some of the other exciting abstracts in the Plenary Session. So we were talking about how this was a big year for lung cancer. There were actually 3 lung cancer studies in the Plenary Session at the Annual Meeting. And let's move on to the second one, LBA4, the LAURA study. This was the first phase 3 study to assess osimertinib, an EGFR tyrosine kinase inhibitor, in patients with EGFR mutant, unresectable stage III non-small cell lung cancer. What are your takeaways from this study?  Dr. Vamsi Velcheti: This is certainly an exciting study, and all of us in the lung community have been kind of eagerly awaiting the results of the study. As you know, for stage III non-small cell lung cancer patients who are unresectable, the standard of care has been really established by the PACIFIC study with the consolidation durvalumab after definitive concurrent chemoradiation. The problem with that study is it doesn't really answer the question of the role of immunotherapy in patients who are never-smokers, and especially in patients who are EGFR positive tumors, where the role of immunotherapy in a metastatic setting has always been questioned. And in fact, there have been several studies as you know, in patients with EGFR mutation positive metastatic lung cancer where immunotherapy has not been that effective. In fact, in the subgroup analysis in the PACIFIC study, patients with EGFR mutation did not really benefit from adding immunotherapy.  So this is an interesting study where they looked at patients with locally advanced, unresectable stage III patients and they randomized the patients 2:1 to osimertinib versus placebo following concurrent or sequential tumor radiation. The primary endpoint for the study was progression free survival, and a total of 216 patients were enrolled and 143 patients received a study treatment, which is osimertinib, and 73 received placebo. And 80% of the patients on the placebo arm crossed over to getting treatment at the time of progression.  So most of us in the lung cancer community were kind of suspecting this would be a positive trial for PFS. But however, I think the magnitude of the difference was truly remarkable. The median PFS in the osimertinib arm was 39.1 months and placebo was 5.6 months and the hazard ratio of 0.16. So it was a pretty striking difference in terms of DFS benefit with the osimertinib consolidation following chemoradiation. So it was truly a positive study for the primary endpoint and the benefit was seen across all the subgroups and the safety was no unexpected safety signals other than a slight increase in the radiation pneumonitis rates in patients receiving osimertinib and other GI and skin tox were kind of as expected. In my opinion, it's truly practice changing and I think patients with EGFR mutation should not be getting immunotherapy consolidation post chemoradiation. Dr. Nate Pennell: I completely agree with you. I think that this really just continues the understanding of the use of osimertinib in EGFR-mutant lung cancer in earlier stages of disease. We know from the ADAURA trial, presented twice in the Plenary at the ASCO Annual Meeting, that for IB, stage II and resectable IIIA, that you prolong progression free or disease free survival. So this is a very similar, comparable situation, but at an even higher risk population or the unresectable stage III patients. I think that the most discussion about this was the fact that the osimertinib is indefinite and that it is distinct from the adjuvant setting where it's being given for three years and then stopped. But I think all of us had some pause when we saw that after three years, especially in the stage III patients from ADAURA, that there were clearly an increase in recurrences after stopping the drug, suggesting that there are patients who are not cured with a time limited treatment, or at least with 3 years of treatment.  The other thing that is sobering from the study, and was pointed out by the discussant, Dr. Lecia Sequist, is if you look at the two-year disease-free survival in the placebo arm, it was only 13%, meaning almost no one was really cured with chemo radiation alone. And that really suggests that this is not that different from a very early stage IV population where indefinite treatment really is the standard of care. I wonder whether you think that's a reasonable approach. Dr. Vamsi Velcheti: I completely agree with you, Nate, and I don't think we cure a majority of our patients with stage III, and less so in patients who have EGFR-mutant, stage III locally advanced. As you just pointed out, I think very few patients actually make it that far along. And I think there's a very high rate of CNS micrometastatic disease or just systemic micrometastatic disease in this population that an effective systemic therapy of osimertinib can potentially have long term outcomes. But again, we perhaps don't cure a vast majority of them. I think that the next wave of studies should incorporate ctDNA and MRD-based assays to potentially identify those patients who could potentially go off osimertinib at some point. But, again, outside of a trial, I would not be doing that. But I think it's definitely an important question to ask to identify de-escalation strategies with osimertinib. And even immunotherapy for that matter, I think we all know that not all patients really require years and years of immunotherapy. They're still trying to figure out how to use immunotherapy in these post-surgical settings, using the MRD to de-escalate adjuvant therapies. So I think we have to have some sort of strategy here. But outside of a clinical trial, I will not be using those assays here to cite treatments, but certainly an important question to ask.  Moving on to the other exciting late-breaking abstracts, LBA5, the ADRIATIC study. This is another study which was also in the plenary session. This study was designed to address this question of consolidation immunotherapy, post chemo radiation for limited-stage small cell cancer, the treatment arms being durvalumab tremelimumab, and durvalumab observation. So what do you think about the study? This study also received a lot of applause and a lot of attention at the ASCO meeting. Dr. Nate Pennell: It was. It was remarkable to be there and actually watch this study as well as the LAURA study live, because when the disease free survival curves and in the ADRIATIC study, the overall survival curves were shown, the speakers were both interrupted by standing ovation of applause just because there was a recognition that the treatment was changing kind of before our eyes. I thought that was really neat. So in this case, I think this is truly a historic study, not necessarily because it's going to necessarily be an earth shakingly positive study. I mean, it was clearly a positive study, but more simply because of the disease in which it was done, and that is limited-stage small cell lung cancer. We really have not had a change in the way we've treated limited-stage small cell lung cancer, probably 25 years. Maybe the last significant advances in that were the advent of concurrent chemotherapy and radiation and then the use of PCI with a very modest improvement in survival. Both of those, I would say, are still relatively modest advances.  In this case, the addition of immunotherapy, which we know helps patients with small cell lung cancer - it's of course the standard of care in combination chemotherapy for extensive stage small cell lung cancer - in this case, patients who completed concurrent chemo radiation were then randomized to either placebo or durvalumab, as well as the third arm of durvalumab tremelimumab, which is not yet been recorded, and co primary endpoints were overall survival and progression free survival. And extraordinarily, there was an improvement in overall survival seen at the first analysis, with a median overall survival of 55.9 months compared to 33.4 months, hazard ratio of 0.73. So highly clinically and statistically significant, that translates at three years to a difference in overall survival of 56.5%, compared to 47.6%, or almost 10% improvement in survival at three years.  There was also a nearly identical improvement in progression-free survival, also with a hazard ratio of 0.76, suggesting that there's a modest number of patients who benefit. But it seems to be a clear improvement with the curves plateauing out. In my opinion, this is very comparable to what we saw with the PACIFIC study in stage III, unresectable non-small cell lung cancer, which immediately changed practice back when that first was reported. And I expect that this will change practice pretty much immediately for small cell as well. Dr. Vamsi Velcheti: Yeah, I completely agree, Nate. I think it's an exciting advance in patients with limited-stage small cell lung cancer. For sure, it's practice-changing, and I think the results were exciting.  So one thing that really intrigued me was in the extensive-stage setting, the benefit was very mediocre with one-to-two month overall survival benefit in both the PACIFIC and in IMpower trial. Here we are seeing almost two-year of median OS benefit. I was kind of puzzled by that, and I thought it may have to do with patients receiving radiation. And we've seen that with the PACIFIC, and makes you wonder if both the CASPIAN and the IMpower studies actually did not allow consolidation thoracic radiation. Hypothetically, if they had allowed consolidation thoracic radiation, perhaps we would have seen better outcomes. Any thoughts on that? Dr. Nate Pennell: We've been trying to prove that radiation and immunotherapy somehow go together better for a long time. Going back to the first description of the abscopal effect, and I'm not sure if I necessarily believe that to be the case, but in this setting where we truly are trying to cure people rather than merely prolong their survival, maybe this is the situation where it truly is more beneficial. I think what we're seeing is something very similar to what we're seen in PACIFIC, where in the stage IV setting, some people have long term survival with immunotherapy, but it's relatively modest. But perhaps in the curative setting, you're seeing more of an impact. Certainly, looking at these curves, we'll have to see with another couple of years to follow up. But a three-year survival of 56% is pretty extraordinary, and I look forward to seeing if this really maintains over the next couple of years follow up.  Moving beyond the Plenary, there were actually lots of really exciting presentations, even outside the Plenary section. One that I think probably got at least as much attention as the ones that we've already discussed today was actually an update of an old trial that's been presented for several prior years. And I'm curious to get your take on why you thought this was such a remarkable study. And we're talking about the LBA8503, which was the 5-year update from the CROWN study, which looked at previously untreated ALK-positive advanced non-small cell in cancer patients randomly assigned to lorlatinib, the third generation ALK inhibitor, versus crizotinib, the first generation ALK inhibitor. What was so exciting about this study, and why were people talking about it?  Dr. Vamsi Velcheti: Yeah, I agree, Nate. We've seen the data in the past, right? Like on the CROWN data, just first like a quick recap. This is the CROWN study, like the phase 3 study of third generation ALK inhibitor lorlatinib. So global randomized phase 3 study in patients with metastatic disease randomized to lorlatinib versus crizotinib, which is a controller. So the primary endpoint was PFS, and we've seen the results in the past of the CROWN readout quoted, with a positive study and the lorlatinib received FDA approval in the frontline setting. But the current study that was presented at the ASCO annual meeting is a kind of a postdoc analysis of five years. The endpoint for the study with central review stopped at three years, and this is actually a follow up beyond that last readout. Interestingly, in this study, when they looked at the median PFS at five years, the lorlatinib arm did not reach a median PFS even at five years and the hazard ratio is 0.19, which is kind of phenomenal in some ways. At 5 years, the majority of the patients were still on the drug. So that's quite incredible. And the benefit was more profound in patients with brain mets with a hazard ratio of 0.08. And again, speaking to the importance of brain penetrant, small molecule inhibitors, and target therapy, the safety profile, there were no additional safety signals noted in the study. We kind of know about the side effects of lorlatinib already from previous studies readouts. No unusual long-term toxicities.  I should note though, about 40% of patients did have CNS, AEs grade 1, 2 CNS toxicities on the  lorlatinib arm. And the other interesting thing that was also reported in the trial was dose reduction of lorlatinib did not have an impact on the PFS, which is interesting in my opinion. They also did some subgroup analysis, biomarker testing, biomarker populations. Patients who had P53 cooperation did much better with lorlatinib versus crizotinib. So overall, the other thing that they also had shown on the trial was the resistance mechanisms that were seen with lorlatinib were very different than what we are used to seeing with the earlier generation ALK inhibitors. The majority of the patients who develop resistance have bypass mechanisms and alterations in MAP kinase pathway PI3K/MTOR/PTEN pathway, suggesting that lorlatinib is a very potent ALK inhibitor and on target ALK mutations don't happen as frequently as we see with the earlier generation ALK inhibitors.  So I think this really begs the question, should we offer lorlatinib to all our patients with metastatic ALK-positive tumors? I think looking at the long-term data, it's quite tempting to say ‘yes', but I think at the same time we have to take into consideration patient safety tolerability. And again, the competitor arm here is crizotinib. So lorlatinib suddenly seems to be, again, cross trial comparisons, but I think the long-term outcomes here are really phenomenal. But at the same time, I think we've got to kind of think about patient because these patients are on these drugs for years, they have to live with all the toxicities. And I think the patient preferences and safety profile matters in terms of what drug we recommend to patients. Dr. Nate Pennell: I completely agree with you. I think the right answer, is that this has to be an individual discussion with patients. The results are incredibly exciting. I mean, the two-year progression free survival was 70%, and the five-year, three years later is still 60%. Only 10% of people are failing over the subsequent three years. And the line is pretty flat. And as you said, even with brain metastases, the median survival is in reach. It's really extraordinary. Moreover, while we do talk about the significant toxicities of lorlatinib, I thought it was really interesting that only 5% of people were supposedly discontinued the drug because of treatment related AEs, which meant that with dose reduction and management, it seems as though most patients were able to continue on the drug, even though they, as you mentioned, were taking it for several years.  That being said, all of us who've had experience with the second-generation drugs like alectinib and brigatinib, compared to the third-generation drug lorlatinib, can speak to the challenges of some of the unique toxicities that go along with it. I don't think this is going to be a drug for everyone, but I do think it is now worth bringing it up and discussing it with the patients most of the time now. And I do think that there will be many people for whom this is going to be a good choice, which is exciting. Dr. Vamsi Velcheti: Absolutely, completely agree. And I think there are newer ALK inhibitors in clinical development which have cleaner and better safety profiles. So we'll have to kind of wait and see how those pan out.  Moving on to the other exciting abstract, LBA8509, the KRYSTAL-12 study. LBA8509 is a phase 3 study looking at adagrasib versus docetaxel in patients with previously treated advanced metastatic non-small cell cancer with KRASG12C mutation. Nate, there's been a lot of hype around this trial. You've seen the data. Do you think it's practice-changing? How does it differentiate with the other drug that's already FDA approved, sotorasib?  Dr. Nate Pennell: Yeah, this is an interesting one. I think we've all been very excited in recent years about the identification of KRASG12C mutations as targetable mutations. We know that this represents about half of KRAS mutations in patients with non-small cell lung cancer, adenocarcinoma, and there are two FDA-approved drugs. Sotorasib was the first and adagrasib shortly thereafter. We already had seen the CodeBreaK 200 study, which was a phase 3 study of sotorasib versus docetaxel that did modestly prolong progression free survival compared to docetaxel, although did not seem to necessarily translate to an improvement in overall survival. And so now, coming on the heels of that study, the KRYSTAL-12 study compared adagrasib, also the KRASG12C  inhibitor versus docetaxel and those with previously treated non-small cell with KRASG12C. And it did significantly improve progression free survival with a hazard ratio of 0.58. Although when you look at the median numbers, the median PFS was only 5.5 months with the adagrasib arm compared to 3.8 months with docetaxel. So while it is a significant and potentially clinically significant difference, it is still, I would say a modest improvement.   And there were some pretty broad improvements across all the different subgroups, including those with brain metastases. It did improve response rate significantly. So 32% response rate without adagrasib, compared to only 9% with docetaxel. It's about what you would expect with chemotherapy. And very importantly, in this patient population, there was activity in the brain with an intracranial overall response rate among those who had measurable brain metastases of 40%. So certainly important and probably that would distinguish it from drugs like docetaxel, which we don't expect to have a lot of intracranial toxicity. There is certainly a pattern of side effects that go along with that adagrasib, so it does cause especially GI toxicity, like diarrhea, nausea, vomiting, transaminitis. All of these were actually, at least numerically, somewhat higher in the adagrasib arm than in docetaxel, a lot more hematologic toxicity with the docetaxel. But overall, the number of serious adverse events were actually pretty well matched between the two groups. So it wasn't really a home run in terms of favorable toxicity with that adagrasib.  So the question is: “In the absence of any data yet on overall survival, should this change practice?” And I'm not sure it's going to change practice, because I do think that based on the accelerated approval, most physicians are already offering the G12C inhibitors like sotorasib and adagrasib, probably more often than chemotherapy, I think based on perceived improvement in side effects and higher response rates, modestly longer progression-free survival, so I think most people think that represents a modest improvement over chemotherapy. And so I think that will continue. It will be very interesting, however, when the overall survival report is out, if it is not significantly better, what the FDA is going to do when they look at these drugs.  Dr. Vamsi Velcheti: Thanks so much. Very well summarized. And I do agree they look more similar than dissimilar. I think CodeBreaK-200 and the KRYSTAL-12, they kind of are very identical. I should say, though I was a little surprised with the toxicity profile of adagrasib. It seemed, I mean, not significantly, but definitely seemed worse than the earlier readouts that we've seen. The GI tox especially seems much worse on this trial. I'm kind of curious why, but if I recall correctly, I think 5% of the patients had grade 3 diarrhea. A significant proportion of patients had grade 3 nausea and vomiting. And the other complicating thing here is you can't use a lot of the antiemetics because of the QT issues. So that's another problem. But I think it's more comparable to sotorasib, in my opinion.  Dr. Nate Pennell: While this is exciting, I like to think of this as the early days of EGFR, when we were using gefitinib and erlotinib. They were certainly advances, but we now have drugs that are much more effective and long lasting in these patients. And I think that the first-generation inhibitors like sotorasib and adagrasib, while they certainly benefit patients, now is just the beginning. There's a lot of research going on, and we're not going to talk about some of the other abstracts presented, but some of the next generation G12C inhibitors, for example, olomorasib, which did have also in the same session, a presentation in combination with pembrolizumab that had a very impressive response rate with potentially fewer side effects, may end up replacing the first generation drugs when they get a little bit farther along. And then moving on to another one, which I think potentially could change practice. I am curious to hear your take on it, was the LBA8505, which was the PALOMA-3 study. This was interesting in that it compared two different versions of the same drug. So amivantamab, the bispecific, EGFR and MET, which is already approved for EGFR exon 20 non-small cell lung cancer, in this case, in more typical EGFR-mutated non-small cell lung cancer in combination with osimertinib with the intravenous amivantamab, compared to the subcutaneous formulation of amivantamab. Why would this be an important study? Dr. Vamsi Velcheti: I found this study really interesting as well, Nate. And as you know, amivantamab has been FDA approved for patients with exon 20 mutation. And also, we've had, like two positive readouts in patients with classical EGFR mutations. One, the MARIPOSA study in the frontline setting and the MARIPOSA-2, in the second-line post osimertinib setting. For those studies, the intravenous amivantamab was used as a treatment arm, and the intravenous amivantamab had a lot of baggage to go along with it, like the infusion reactions and VTEs and other classic EGFR related toxicity, skin toxicities. So the idea behind developing the subcutaneous formulation of amivantamab was mainly to reduce the burden of infusion, infusion time and most importantly, the infusion related reactions associated with IV formulation.  In a smaller phase 2 study, the PALOMA study, they had looked at various dosing schemas like, subcutaneous formulation, and they found that the infusion related reactions were very, very low with the subcutaneous formulation. So that led to the design of this current study that was presented, the PALOMA-3 study. This was for patients who had classical EGFR mutations like exon 19, L858R. The patients were randomized 1:1 to subcutaneous amivantamab with lazertinib versus IV amivantamab plus lazertinib. The endpoints for the study, it's a non-inferiority study with co primary endpoints of C trough and C2 AUC, Cycle 2 AUC. They were looking at those pharmacological endpoints to kind of demonstrate comparability to the IV formulation. So in this study, they looked at these pharmacokinetic endpoints and they were essentially identical. Both subcutaneous and IV formulations were compatible. And in terms of clinical efficacy as well, the response rate was identical, no significant differences. Duration of response was also identical. The PFS also was comparable to the IV formulation. In fact, numerically, the subcutaneous arm was a little better, though not significant. But it appears like, you know, the overall clinical and pharmacological profile of the subcutaneous amivantamab was comparable. And most interestingly, the AE profile, the skin toxicity was not much different. However, the infusion reactions were substantially lower, 13% with the subcutaneous amivantamab and 66% with IV amivantamab. And also, interestingly, the VTE rates were lower with the subcutaneous version of amivantamab. There was still a substantial proportion of patients, especially those who didn't have prophylactic anticoagulation. 17% of the patients with the subcutaneous amivantamab had VTE versus 26% with IV amivantamab. With prophylaxis, which is lower in both IV and subcutaneous, but still subcutaneous formulation at a lower 7% versus 12% with the IV amivantamab.  So overall, I think this is an interesting study, and also the authors had actually presented some interesting data on administration time. I've never seen this before. Patients reported convenience using a modified score of patient convenience, essentially like patients having to spend a lot of time in the infusion site and convenience of the patient getting the treatment. And it turns out, and no surprise, that subcutaneous amivantamab was found to be more convenient for patients.  So, Nate, I want to ask you your take on this. In a lot of our busy infusion centers, the time it takes for those patients to get the infusion does matter, right? And I think in our clinic where we are kind of fully booked for the infusion, I think having the patients come in and leave in 15, 20 minutes, I think it adds a lot of value to the cancer center operation.  Dr. Nate Pennell: Oh, I completely agree. I think the efficacy results were reassuring. I think the infusion related reaction difference, I think is a huge difference. I mean, I have given a fair amount of amivantamab, and I would say the published IRR rate of 66%, 67% I would say, is maybe even underestimates how many patients get some kind of reaction from that, although it really is a first dose phenomenon. And I think that taking that down to 13% is a tremendous advance. I think fusion share time is not trivial as we get busier and busier. I know our cancer center is also very full and it becomes challenging to schedule people, and being able to do a five-minute treatment versus a five-hour treatment makes a big difference for patients.  It's interesting, there was one slide that was presented from an efficacy standpoint. I'm curious about your take on this. They showed that the overall survival was actually better in the subcu amivantamab arm, hazard ratio of 0.62. Now, this was only an exploratory endpoint. They sort of talk about perhaps some rationale for why this might be the case. But at the very least, I think we can be reassured that it's not less effective to give it and does seem to be more tolerable and so I would expect that this hopefully will be fairly widely adopted. Dr. Vamsi Velcheti: Yeah, I agree. I think this is a welcome change. Like, I think the infusion reactions and the resources it takes to get patients through treatments. I think it's definitely a win-win for patients and also the providers.  And with that, we come to the conclusion of the podcast. Nate, thank you so much for the fantastic insights today. Our listeners will find all the abstracts discussed today in the transcripts of the episode. Thank you so much for joining us today, Dr. Pennell.  Dr. Nate Pennell: Oh, thanks for inviting me. It's always fun to talk about all these exciting advances for our patients. Dr. Vamsi Velcheti: Thanks to our listeners for your time today. You will find links to all the abstracts discussed today in the transcript of the episode. Finally, if you value the insights that you hear from ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcast.   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.   Find out more about today's speakers:    Dr. Vamsi Velcheti  @VamsiVelcheti    Dr. Nathan Pennell  @n8pennell    Follow ASCO on social media:      @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures:  Dr. Vamsi Velcheti:  Honoraria: ITeos Therapeutics  Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus  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. Nathan Pennell:    Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron   Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi

Dr. Jyoti Patel discusses the latest update to the stage IV NSCLC with driver alterations living guideline, specifically for patients with EGFR or ROS1 alterations. She shares the latest recommendations based on recently published evidence, such as the FLAURA2, MARIPOSA-2, and TRIDENT-1 trials. Dr. Patel talks about how to choose between these new options and the impact for patients living with stage IV NSCLC, as well as novel drugs the panel is monitoring for future guideline updates. Read the full living guideline update “Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.1” at www.asco.org/living-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/living-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.24.00762  Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows, including this one at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Jyoti Patel from Northwestern University, co-chair on, “Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.1.”  Thank you for being here today, Dr. Patel. Dr. Jyoti Patel: Thanks so much.   Brittany Harvey: Then, before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Patel, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes.  So then to dive into the content of why we're here today, Dr. Patel, this living clinical practice guideline for systemic therapy for patients with stage four non-small cell lung cancer with driver alterations is being updated on a regular basis. So what prompted the update to the recommendations in this latest update?  Dr. Jyoti Patel: This recent update, I think, absolutely reflects how quickly the science is changing. The landscape of treatment options for patients with advanced non-small cell lung cancer is evolving so rapidly, and guidelines from even six months ago don't address some of the newest approvals and newest data and the newest clinical scenarios that we're presented with when we see patients. I think it's harder because before there was usually a single answer, and now there are a number of scenarios, and we hope that the guideline addresses this. Brittany Harvey: Absolutely. The panel's had a lot of data to review as you keep this guideline up to date.  So then this latest update addresses updates to both EGFR and ROS1 alterations. So starting with EGFR, what are the updated recommendations for patients with stage four non-small cell lung cancer and an EGFR exon 19 deletion or exon 21 L858R substitution?  Dr. Jyoti Patel: So for patients with classical driver mutations in EGFR, our recommendation remains that patients should be offered osimertinib. We now also have data to support intensification of therapy with osimertinib and chemotherapy. The FLAURA2 trial was a global randomized study in which patients with classical mutations were assigned to receive either osimertinib or osimertinib with doublet chemotherapy. The trial showed that progression free survival was longer with osimertinib plus chemotherapy with a hazard ratio that was pretty profound, 0.62. In patients who had CNS metastasis as well as patients with L858R mutations, this benefit remained and was perhaps even greater. Now the study remains immature in terms of OS. What we can say is that chemotherapy adds toxicity, so the inconvenience of 13 weekly infusions, expected toxicities from chemotherapy of myelosuppression and fatigue. I think this- we'll continue to watch as the study matures to really see the OS benefit, but certainly intensification in the frontline setting is an option for patients.  The other major update was for second and subsequent line therapy for these patients with EGFR mutations. Another important trial, a study called MARIPOSA-2, was published in the interim, and this was for patients who had received osimertinib in the frontline setting. Patients were randomized to one of three arms. The two arms that are most relevant for us to discuss are chemotherapy with amivantamab or chemotherapy alone. Chemotherapy with amivantamab was associated with an improvement in progression free survival with a hazard ratio of 0.48 as well as improvements in response rate with almost a doubling of response rate to the mid 60%. There was certainly an increase in AEs associated with amivantamab, primarily rash and lower extremity edema and importantly infusion reaction. Based on this data, though in the superior PFS and response rate, we've said that patients after osimertinib should be offered chemotherapy plus amivantamab. Patients may opt for chemotherapy alone because of the toxicity profile, but this recent update is reflective of that data. Brittany Harvey: Excellent. Thank you for reviewing those updated recommendations and the supporting evidence behind those recommendations. I think that's important to the nuance and the toxicity associated with these new recommendations as well.   So then, following those recommendations, what are the updated recommendations for patients with stage four non-small cell lung cancer and a ROS1 rearrangement? Dr. Jyoti Patel: ROS1 fusions have been noted in a small but important subset of patients. We now reflect multiple new options for patients. Traditionally, crizotinib was the primary drug that was recommended, but we now have two very active drugs, repotrectinib, and entrectinib, that have both been FDA approved. Repotrectinib was approved based on a study called the TRIDENT-1 trial. In this study, patients who were treatment naive, who had not received a prior TKI, had a response rate of 79% and a long duration of response over 34 months. For patients who had received prior TKIs, so primarily crizotinib, the response rate was lower at 38%. But again, very clinically meaningful. Repotrectinib has known CNS activity, so it would be the favored drug over crizotinib, which doesn't have CNS penetration. The decision between entrectinib and repotrectinib is one, I think, based on toxicity. Repotrectinib can cause things like dizziness and hypotension. Entrectinib can cause weight gain, and also has CNS effects. Brittany Harvey: Appreciate you reviewing those recommendations as well.  So then you've already talked a little bit about this in terms of deciding between some of the options. But in your view, what should clinicians know as they implement these new recommendations, and how do these new recommendations fit into the previous recommendations? Dr. Jyoti Patel: So there's an onslaught of new data, and certainly many of us want to remain at the front of our fields and prescribe the newest drug, our most effective drug, to all of our patients. But for the person living with cancer and in the practice of medicine, I think it's much more nuanced than that. For example, for a patient with an EGFR mutation exon deletion 19, the expectation is that osimertinib will have a deep and durable response. Certainly a patient will eventually have progression. I think the decision about intensification of therapy and chemotherapy on the onset really has to do with how much the patient is willing to deal with the inconvenience of ongoing chemotherapy, the uncertainty about what comes next after progression on chemotherapy. It may be, though, that a patient may very much fear progressive disease, and so that inconvenience is lessened because anxiety around feeling like they're doing everything for their cancer is diminished by intensification of therapy. Others who may have a large volume of disease or profoundly symptomatic, or who have L858R or brain metastasis it may make sense to give chemotherapy again, we're improving the time until progression significantly by combination therapy. Brittany Harvey: Definitely those nuances are important as we think about which options that patients should receive, along with shared decision making as well.  So then what do these new options mean for patients with EGFR or ROS1 alterations? Dr. Jyoti Patel: It's fantastic for patients that there are multiple options. It's also really hard for patients that there are multiple options, because then again, we have to really clarify aims of therapy, identify what's really important in patient experience and the lived importance of treatment delivery and the burden of treatment delivery. Now more than ever, oncologists have to know what's new and exciting. But patients have to be willing to ask and participate in the shared decision making - understanding their cancer and understanding that their options are absolutely important. As patients start making their decisions, we have the data just in terms of trial outcomes. I think we're now trying to understand the burden of treatment for patients. And so that piece of communicating financial toxicity, long term cumulative lower grade toxicity is going to be more important than ever. Brittany Harvey: Absolutely. It's great to have these new options, and those elements of communication are key to ensuring that patients meet their goals of care.  So then finally, as this is a living guideline, what ongoing research is the panel monitoring for future updates to these recommendations for patients with stage four non-small cell lung cancer with driver alterations? Dr. Jyoti Patel: It's certainly been an exciting time, and that's primarily because we've been able to build on years of foundational science and we have new drugs. Patients have been willing to volunteer to go on clinical trials and to think about what treatment options may be best. Now, the work really comes on seeing the longer term outcomes from these trials. So looking at these trials for overall survival, we want to also better identify which patients will benefit the most from these treatments and so that might be additional biomarker analysis. So it may be that we can identify patients that may need intensification of therapy based on tumor factors as well as patient factors as well in those patients in whom we can de-escalate treatment. I think there are a number of new compounds that are in the pipeline. So fourth generation EGFR TKIs are certainly interesting. They may be able to overcome resistance for a subset of patients who progress on osimertinib. We also think about novel drugs such as antibody drug conjugates and how they'll fit into our paradigm with osimertinib or after carboplatin-based doublets. Brittany Harvey: Definitely. We'll look forward to both longer term readouts from the current trials and new trials in this field to look at additional options for patients.  So I want to thank you so much for your time today, Dr. Patel, and thank you for all of your work to keep this living guideline up to date. Dr. Jyoti Patel: Great. Thanks so much, Brittany. It really is an exciting time for people who treat lung cancer and for patients who have lung cancer. We certainly have a long way to go, but certainly the rapid uptake of these guidelines reflect the progress that's being made.  Brittany Harvey: Absolutely. And just a final thank you to all of our listeners for tuning into the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/living-guidelines.  You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. 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.      

Last week, the Food and Drug Administration (FDA) approved four different therapies in the oncology space — one of which, Amtagvi, marks the first cellular therapy for the treatment of solid cancers.  The week's first approval (an Onivyde regimen for metastatic pancreatic cancer) was covered in last week's episode, but here's a list of what has happened since that last recording.  FDA Approves Tepmetko for Metastatic NSCLC Subtype Patients with metastatic non-small cell lung cancer that has MET exon 14 skipping alterations may soon have a new treatment option, as the FDA approved Tepmetko in this indication.  Notably, this full approval is coming three years after the agency's accelerated approval of the agent back in February 2021. Follow-up clinical trial data showed that 57% of previously untreated patients responded to therapy with Tepmetko, with 40% having a duration of response that lasted a year or longer.  FDA Approves Amtagvi for Pretreated, Advanced Melanoma  On Feb. 16, the FDA approved Amtagvi for patients with advanced melanoma who had previously been treated with an immunotherapy or targeted therapy. Notably, Amtagvi is a cell-based therapy and is actually the first cell-based treatment to be approved in the solid tumor space.  According to trial results that led to the approval, 31.5% of patients responded to therapy. Now this is a pretty exciting number, considering that this heavily pretreated population tends to have low response rates. Not to mention, TIL therapies like Amtagvi — while upfront they require about a three-week hospital stay — may set patients up for years without having to undergo more treatment, according to Dr. Rodabe Amaria from The University of Texas MD Anderson Cancer Center, who I spoke with after the approval.   Tagrisso Plus Chemo Approved by FDA for EGFR-Mutated NSCLC In the lung cancer space, we saw the approval of Tagrisso plus platinum-based chemotherapy for patients with locally advanced or metastatic non-small cell lung cancer whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations.  Findings from the FLAURA 2 trial led to this approval, as data showed that progression-free survival was 25.5 months for patients who received Tagrisso plus chemotherapy, compared to 16.7 months for patients who received Tagrisso alone. Overall survival data is still immature at this point — meaning that the researchers just don't have enough data to calculate averages — so stay tuned for more on that.  For more news on cancer updates, research and education, don't forget to subscribe to CURE®'s newsletters here.

Lung cancer is a significant global health issue, being the second most commonly diagnosed cancer and the leading cause of cancer-related death worldwide. Non-small-cell lung cancer (NSCLC) represents the majority of lung cancer cases and is often diagnosed at an advanced stage. Epidermal growth factor receptor (EGFR) mutations are more common in Asian NSCLC populations than in Western populations. Activating EGFR mutations, such as exon 19 deletions and L858R, are predictive of response to tyrosine kinase inhibitors (TKIs) and have revolutionized the treatment landscape for patients with EGFR-mutated NSCLC. However, most clinical trials tend to lack data for the elderly population, even though a significant proportion of lung cancer patients are aged 65 years and older. This underrepresentation of elderly patients in clinical trials limits our understanding of the effectiveness and safety of EGFR-TKIs in this specific population. In this new study, researchers Ling-Jen Hung, Ping-Chih Hsu, Cheng-Ta Yang, Chih-Hsi Scott Kuo, John Wen-Cheng Chang, Chen-Yang Huang, Ching-Fu Chang, and Chiao-En Wu from Chang Gung University and Taoyuan General Hospital conducted a multi-institute retrospective study to investigate the effectiveness and safety of afatinib, gefitinib, and erlotinib for treatment-naïve elderly patients with EGFR-mutated advanced NSCLC. On January 8, 2024, their research paper was published in Aging's Volume 16, Issue 1, entitled, “Effectiveness and safety of afatinib, gefitinib, and erlotinib for treatment-naïve elderly patients with epidermal growth factor receptor-mutated advanced non-small-cell lung cancer: a multi-institute retrospective study.” Full blog - https://aging-us.org/2024/01/efficacy-and-safety-of-egfr-tkis-for-elderly-patients-with-nsclc/ Paper DOI - https://doi.org/10.18632/aging.205395 Corresponding author - Chiao-En Wu - 8805017@cgmh.org.tw Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205395 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, elderly patients, epidermal growth factor receptor, tyrosine kinase inhibitor, non-small-cell lung cancer, real-world evidence About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.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 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.

Dr. Navneet Singh joins us again, this time to discuss the rapid recommendation update for stage III non-small cell lung cancer, incorporating updated data presented at the 2023 ASCO Annual Meeting. He discusses the new trials that prompted the guideline update and updated recommendations on adjuvant osimertinib for patients with EGFR exon 19 deletion or exon 21 L858R mutation, and the option of neoadjuvant chemoimmunotherapy for patients with stage III NSCLC. Read the update, "Management of Stage III Non-Small Cell Lung Cancer: ASCO Guideline Rapid Recommendation Update" at www.asco.org/thoracic-cancer-guidelines TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/thoracic-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest disclosures in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.23.01261 Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts.  My name is Brittany Harvey, and today I'm interviewing Dr. Navneet Singh from the Postgraduate Institute of Medical Education and Research in Chandigarh, India, Co-chair on “Management of Stage III Non-Small Cell Lung Cancer: ASCO Guideline Rapid Recommendation Update.”  Thank you for being here, Dr. Singh. Dr. Navneet Singh: Thank you for having me. Brittany Harvey: Then, before we discuss this guideline, I'd just like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Singh, who is joining us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes.  So then, to dive into the content of this guideline, first, Dr. Singh, what prompted this rapid update to the ASCO management of stage III non-small cell lung cancer, which was initially published in 2021? Dr. Navneet Singh: There have been a number of studies that have involved patients with stage III non-small cell lung cancer since the publication of the stage III NSCLC management guidelines. Of note, three trials deserve special recognition and have actually formed the basis for this rapid update. These include the ADAURA trial for use of osimertinib as adjuvant treatment for completely resected stages Ib to IIIa NSCLC and harboring a sensitizing EGFR mutation. The other two trials have explored the use of PD-1 immune checkpoint inhibitor therapy in combination with chemotherapy as neoadjuvant treatment of potentially resectable stages I to III NSCLC. And these are the CheckMate 816 trial with nivolumab and the KEYNOTE-671 trial with pembrolizumab. Brittany Harvey: Great, thank you for that background. So then, based off these three new trials that you just mentioned, what are the updated recommendations issued in this rapid recommendation update? Dr. Navneet Singh: The first updated recommendation is based on the overall survival benefit observed in the ADAURA trial. And this recommendation is that patients with dissected stage III NSCLC and harboring an EGFR exon 19 deletion or an exon 21 L858R mutation should be offered adjuvant osimertinib after platinum-based chemotherapy. The second important update is that in the absence of contraindications, patients with stage III non-small cell lung cancer who are planned for surgical resection should receive a neoadjuvant combination of a platinum doublet chemotherapy, and immunotherapy. Now, both of these are based on high-quality evidence and have a strong strength of recommendation. Brittany Harvey: Understood. I appreciate you reviewing both the level of evidence and the strength of the recommendation for those as well. So then, what should clinicians know as these new recommendations are implemented? Dr. Navneet Singh: Now, it's very important for clinicians involved in the management of lung cancer to realize the importance of biomarker testing, something that was initially believed to have relevance only for metastatic disease. But now, with the availability of data indicating the benefit of immunotherapy and targeted therapy not just in metastatic disease but also in early-stage as well as locally advanced disease, clinicians need to ensure that biomarker testing, especially EGFR mutation and PD-L1 expression by approved and validated methods is performed in all patients with stages I to  III non-small cell lung cancer. This is important to decide and select patients for the appropriate biological therapy, which is either targeted therapy or immunotherapy that can be used in conjunction with or following chemotherapy. I need to clarify here that the spectrum of biomarker testing that is recommended for metastatic disease is much larger than what is currently being advocated for early or locally advanced NSCLC. Brittany Harvey: Great, and I appreciate that clarification. So then you've just described what this guideline means for clinicians, but how does this rapid update impact patients diagnosed with stage III non-small cell lung cancer? Dr. Navneet Singh: Well, for patients with stage III non-small cell lung cancer, all the three trials that form the basis for this rapid update indicate very encouraging developments. The neoadjuvant chemo-immunotherapy approach is now the standard of care for potentially resectable stage III disease, as this combination has been shown to be superior to chemotherapy alone in terms of higher probability of achieving a complete or major pathological tumor response, as well as improving recurrence or event-free survival following surgical resection. Similarly, adjuvant osimertinib for resected stage III NSCLC patients having a sensitizing EGFR mutation has been shown to significantly improve overall survival compared to placebo. It is important to highlight here that osimertinib treatment in stage III NSCLC should be initiated following the completion of adjuvant chemotherapy. Brittany Harvey: Understood. So then this panel works to rapidly update this guideline, turning it around after the ASCO Annual Meeting. But what are the ongoing research developments that the panel is monitoring for future guideline updates? Dr. Navneet Singh: Well, the expert panel is eagerly awaiting overall survival data from the neoadjuvant chemo-immunotherapy trials. We have several unanswered questions which ongoing research will attempt to answer. And some of these questions include number one, whether adjuvant immunotherapy is beneficial for patients who have already received neoadjuvant chemo-immunotherapy, and if so, what is the optimal duration for the same? Second, is the three-year adjuvant osimertinib duration appropriate? Can lesser duration of treatment suffice for a subgroup of patients? And if so, it would lead to a reduction in both treatment costs as well as a reduction in potential treatment-related adverse effects. On the other hand, other patients in whom stopping at three years may not be warranted, and should patients with exon 19 deletion be treated differently from those with exon 21 L858R mutation? Third, does a similar adjuvant targeted therapy approach be warranted for ALK-rearranged NSCLC that has been surgically resected? And fourth, are there specific subgroups of patients undergoing neoadjuvant treatment in whom immunotherapy as a neoadjuvant treatment may not be effective? Examples are those with EGFR mutations or ALK rearrangements, or even those with no PD-L1 expression. Brittany Harvey: Absolutely. We'll look forward to finding the answer to those questions for future guideline updates. So I want to thank you so much for your work to rapidly update this guideline and thank you for your time today, Dr. Singh. Dr. Navneet Singh: Pleasure. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store.  If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. 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.  

Dr. Navneet Singh highlights the latest evidence-based recommendation updates from the ASCO living guideline on stage IV non-small cell lung cancer with driver alterations. This update focuses on new second-line options for patients with advanced NSCLC and an EGFR exon 20 insertion, including amivantamab and mobocertinib. Dr. Singh also discusses updated results from CodeBreaK 200 and the option of second-line therapy with sotorasib for patients with advanced NSCLC and a KRAS-G12C mutation. Read the update, “Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2023.2” and view all recommendations at www.asco.org/living-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/living-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest disclosures in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.23.01055  Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one at asco.org/podcasts.   My name is Brittany Harvey, and today I am joined by Dr. Navneet Singh from the Postgraduate Institute of Medical Education and Research in Chandigarh, India, co-chair on “Therapy for Stage IV Non-Small Cell Lung Cancer with Driver Alterations: ASCO Living Guideline, Version 2023.2.” Thank you for being here, Dr. Singh.  Dr. Navneet Singh: Thank you for having me, Brittany. Brittany Harvey: Before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the Guideline panel, including Dr. Singh, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes.  So then, to dive into this living clinical practice guideline, Dr. Singh, this living guideline for systemic therapy for stage IV non-small cell lung cancer with driver alterations is being routinely updated. What new studies were reviewed by the panel to prompt an update to the recommendations in this version? Dr. Navneet Singh: So for this 2023 version 2 update, three trials were included. These include two studies which involved patients with exon 20 insertion mutations, who had received prior platinum-based chemotherapy and subsequently were treated with either amivantamab in the CHRYSALIS trial or with mobocertinib in the EXCLAIM trial. The third trial which formed the basis for this update was one which involved patients with KRAS G12C mutation who had previously received systemic therapy and subsequently were treated with sotorasib. And this was the CodeBreaK 200 trial. Brittany Harvey: Understood. So then, based on these three new trials that you've just mentioned, what are the updated recommendations from the expert panel for patients with advanced non-small cell lung cancer? Dr. Navneet Singh: For patients with advanced NSCLC with an EGFR exon 20 insertion mutation and an ECOG performance status of 0 to 2 who have received prior platinum-based chemotherapy, clinicians may offer amivantamab or mobocertinib as monotherapy. It is important to mention here that in the absence of head-to-head comparison of amivantamab or mobocertinib with each other or with other standard second-line therapies, no recommendation for sequencing can be made and therefore treatment should be individualized. Now, use of either of the two drugs is based on low-quality evidence and has a weak strength of recommendation. And the updates for treating KRAS G12C-mutated NSCLC is largely similar; that patients who have received prior systemic therapy may be offered sotorasib.  Brittany Harvey: Thank you for reviewing those updated recommendations. So what should clinicians know as they implement these new recommendations and how do they interface with the existing recommendations? Dr. Navneet Singh: It is important for clinicians involved in the management of EGFR mutant lung cancer to realize that exon 20 insertions are the third most common group of EGFR mutations and comprise approximately 5% of all EGFR mutations. Now, historically, the EGFR targeted drugs which have been the first, second, or third generation tyrosine kinase inhibitors have largely shown efficacy for the two common types of EGFR mutations, namely the exon 19 deletions and the exon 21 L858R point mutation. Exon 20 insertion mutations thus did not have any effective targeted therapy so far. But now, both of these drugs, amivantamab and mobocertinib, have shown very promising results for pretreated patients with this molecular aberration and therefore may be used in view of standard second line therapy. Similarly, in the case of KRAS G12C mutation, before this, there was no effective targeted therapy, but now sotorasib, based on the CodeBreaK 200 trial, appears to be a very valid option in view of standard second-line therapy.  Brittany Harvey: Excellent. So then, what do these new treatment options mean for patients with stage IV non-small cell lung cancer and an exon 20 insertion or a KRAS G12C mutation?  Dr. Navneet Singh: For patients with stage IV NSCLC and harboring an EGFR exon 20 insertion, the availability of two specific targeted drugs will improve the treatment options available following standard first-line therapy. Furthermore, ongoing trials for these agents in the treatment-naive setting may eventually lead to a scenario wherein such patients may be treated upfront with targeted therapy rather than chemotherapy or chemoimmunotherapy, analogous to how patients with the common EGFR mutations are treated. The ultimate aim of precision medicine is to offer the most effective treatment based on biomarker expression and targeted therapies in comparison to chemotherapy because these lead to better treatment outcomes and lesser side effects. Brittany Harvey: Absolutely. The goal of better outcomes with less side effects is what we're looking to achieve here. So then, finally, as this is a living guideline, what emerging therapies or targets is the panel monitoring for future guideline updates? Dr. Navneet Singh: As was already said, the expert panel eagerly awaits data from ongoing trials which are assessing the efficacy of drugs targeting the EGFR exon 20 insertion mutations, namely amivantamab and mobocertinib as first-line therapy, as also the drugs which target the KRAS G12C mutations which is sotorasib and adagrasib in the treatment-naïve setting. Ultimately, the optimal sequencing of therapies needs to be established in advanced and metastatic non-small cell lung cancer for several of the oncogenic driver alterations other than classical EGFR mutations and ALK and ROS-1 rearrangements. These include the EGFR exon 20 insertions and other uncommon EGFR mutations, the BRAF V600E, KRAS G12C, the HER2, and the MET exon 14 skipping mutations as well as the RET and NTRK fusions.  Brittany Harvey: It sounds like the living guideline expert panel will be busy moving forward then. So I want to thank you so much for your work to update this living guideline and thank you for your time today, Dr. Singh.  Dr. Navneet Singh:  Thank you so much, it was a pleasure being here. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/living-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. 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.  

CME credits: 1.00 Valid until: 29-06-2024 Claim your CME credit at https://reachmd.com/programs/cme/axis-nsclc-cme-broadcast-replay/15338/ Capitalizing on the advances in the identification of oncogenic driver mutations, genetic testing, and therapeutic approaches that target actionable mutations, targeted therapies are the current standard of care for eligible patients with advanced non–small cell lung cancer (NSCLC). Many targeted therapies are approved for the treatment of metastatic NSCLC with oncologic therapy decisions based on the presence of mutations and gene rearrangements. The National Comprehensive Cancer Center (NCCN) Clinical Practice Guidelines for metastatic NSCLC outline recommendations for molecular testing, now including EGFR mutation (for examples, exon 19 deletion or L858R), EGFR exon 20 insertion mutation, KRAS G12C mutation, ALK rearrangement, ROS1 rearrangement, BRAF-V600E mutation, NTRK1/2/3 gene fusion, METex14 skipping mutation, and RET rearrangement, along with PD-L1 expression level in patients with advanced or metastatic NSCLC. The development of these newer and other investigational targeted therapies provides unprecedented opportunities for improving outcomes for patients with targetable mutations. This educational activity will address the incorporation of appropriate and timely use of guideline-recommended biomarker testing and optimization of targeted and personalized treatment of patients with NSCLC. =

Go online to PeerView.com/DCG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The time has come for even more precision in testing and targeted treatment of NSCLC. EGFR-mutated lung cancer is a perfect example of this need. The term "EGFR-positive lung cancer” is no longer adequate or specific enough to characterize this complex molecular subtype of lung cancer. Increased granularity is needed for both biomarker testing and targeted treatment selection for patients with different types of EGFR mutations. New agents and combinations have become available for patients with common (eg, exon 19 deletion, exon 21 L858R) and uncommon (eg, exon 20 insertions) EGFR mutations, and more are on the horizon. Novel strategies for overcoming resistance to EGFR-targeted therapies are showing great promise as well. This PeerView Live educational activity, based on a recent live symposium, explores the latest advances and future directions in biomarker-driven, individualized therapy for patients with NSCLC harboring common and less common EGFR mutations through engaging discussions and challenging case-based debates. Upon completion of this activity, participants should be better able to: Characterize the different types of EGFR mutations in NSCLC, their role as therapeutic targets, and evidence supporting the use of current and emerging targeted therapies or combinations for NSCLC with various common or uncommon EGFR mutations; Collaborate with the multidisciplinary team to promote widespread biomarker testing in patients with NSCLC, select appropriate tests to detect common and less common EGFR mutations, and ensure accurate interpretation of results to guide targeted therapy selection; and Apply current evidence and guidelines to individualize targeted therapy for patients with NSCLC exhibiting different EGFR mutations based on the efficacy and safety profile of the therapies, disease characteristics, and patient needs and preferences.

Go online to PeerView.com/DCG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The time has come for even more precision in testing and targeted treatment of NSCLC. EGFR-mutated lung cancer is a perfect example of this need. The term "EGFR-positive lung cancer” is no longer adequate or specific enough to characterize this complex molecular subtype of lung cancer. Increased granularity is needed for both biomarker testing and targeted treatment selection for patients with different types of EGFR mutations. New agents and combinations have become available for patients with common (eg, exon 19 deletion, exon 21 L858R) and uncommon (eg, exon 20 insertions) EGFR mutations, and more are on the horizon. Novel strategies for overcoming resistance to EGFR-targeted therapies are showing great promise as well. This PeerView Live educational activity, based on a recent live symposium, explores the latest advances and future directions in biomarker-driven, individualized therapy for patients with NSCLC harboring common and less common EGFR mutations through engaging discussions and challenging case-based debates. Upon completion of this activity, participants should be better able to: Characterize the different types of EGFR mutations in NSCLC, their role as therapeutic targets, and evidence supporting the use of current and emerging targeted therapies or combinations for NSCLC with various common or uncommon EGFR mutations; Collaborate with the multidisciplinary team to promote widespread biomarker testing in patients with NSCLC, select appropriate tests to detect common and less common EGFR mutations, and ensure accurate interpretation of results to guide targeted therapy selection; and Apply current evidence and guidelines to individualize targeted therapy for patients with NSCLC exhibiting different EGFR mutations based on the efficacy and safety profile of the therapies, disease characteristics, and patient needs and preferences.

Go online to PeerView.com/DCG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The time has come for even more precision in testing and targeted treatment of NSCLC. EGFR-mutated lung cancer is a perfect example of this need. The term "EGFR-positive lung cancer” is no longer adequate or specific enough to characterize this complex molecular subtype of lung cancer. Increased granularity is needed for both biomarker testing and targeted treatment selection for patients with different types of EGFR mutations. New agents and combinations have become available for patients with common (eg, exon 19 deletion, exon 21 L858R) and uncommon (eg, exon 20 insertions) EGFR mutations, and more are on the horizon. Novel strategies for overcoming resistance to EGFR-targeted therapies are showing great promise as well. This PeerView Live educational activity, based on a recent live symposium, explores the latest advances and future directions in biomarker-driven, individualized therapy for patients with NSCLC harboring common and less common EGFR mutations through engaging discussions and challenging case-based debates. Upon completion of this activity, participants should be better able to: Characterize the different types of EGFR mutations in NSCLC, their role as therapeutic targets, and evidence supporting the use of current and emerging targeted therapies or combinations for NSCLC with various common or uncommon EGFR mutations; Collaborate with the multidisciplinary team to promote widespread biomarker testing in patients with NSCLC, select appropriate tests to detect common and less common EGFR mutations, and ensure accurate interpretation of results to guide targeted therapy selection; and Apply current evidence and guidelines to individualize targeted therapy for patients with NSCLC exhibiting different EGFR mutations based on the efficacy and safety profile of the therapies, disease characteristics, and patient needs and preferences.

Go online to PeerView.com/DCG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The time has come for even more precision in testing and targeted treatment of NSCLC. EGFR-mutated lung cancer is a perfect example of this need. The term "EGFR-positive lung cancer” is no longer adequate or specific enough to characterize this complex molecular subtype of lung cancer. Increased granularity is needed for both biomarker testing and targeted treatment selection for patients with different types of EGFR mutations. New agents and combinations have become available for patients with common (eg, exon 19 deletion, exon 21 L858R) and uncommon (eg, exon 20 insertions) EGFR mutations, and more are on the horizon. Novel strategies for overcoming resistance to EGFR-targeted therapies are showing great promise as well. This PeerView Live educational activity, based on a recent live symposium, explores the latest advances and future directions in biomarker-driven, individualized therapy for patients with NSCLC harboring common and less common EGFR mutations through engaging discussions and challenging case-based debates. Upon completion of this activity, participants should be better able to: Characterize the different types of EGFR mutations in NSCLC, their role as therapeutic targets, and evidence supporting the use of current and emerging targeted therapies or combinations for NSCLC with various common or uncommon EGFR mutations; Collaborate with the multidisciplinary team to promote widespread biomarker testing in patients with NSCLC, select appropriate tests to detect common and less common EGFR mutations, and ensure accurate interpretation of results to guide targeted therapy selection; and Apply current evidence and guidelines to individualize targeted therapy for patients with NSCLC exhibiting different EGFR mutations based on the efficacy and safety profile of the therapies, disease characteristics, and patient needs and preferences.

Go online to PeerView.com/DCG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The time has come for even more precision in testing and targeted treatment of NSCLC. EGFR-mutated lung cancer is a perfect example of this need. The term "EGFR-positive lung cancer” is no longer adequate or specific enough to characterize this complex molecular subtype of lung cancer. Increased granularity is needed for both biomarker testing and targeted treatment selection for patients with different types of EGFR mutations. New agents and combinations have become available for patients with common (eg, exon 19 deletion, exon 21 L858R) and uncommon (eg, exon 20 insertions) EGFR mutations, and more are on the horizon. Novel strategies for overcoming resistance to EGFR-targeted therapies are showing great promise as well. This PeerView Live educational activity, based on a recent live symposium, explores the latest advances and future directions in biomarker-driven, individualized therapy for patients with NSCLC harboring common and less common EGFR mutations through engaging discussions and challenging case-based debates. Upon completion of this activity, participants should be better able to: Characterize the different types of EGFR mutations in NSCLC, their role as therapeutic targets, and evidence supporting the use of current and emerging targeted therapies or combinations for NSCLC with various common or uncommon EGFR mutations; Collaborate with the multidisciplinary team to promote widespread biomarker testing in patients with NSCLC, select appropriate tests to detect common and less common EGFR mutations, and ensure accurate interpretation of results to guide targeted therapy selection; and Apply current evidence and guidelines to individualize targeted therapy for patients with NSCLC exhibiting different EGFR mutations based on the efficacy and safety profile of the therapies, disease characteristics, and patient needs and preferences.

Go online to PeerView.com/DCG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The time has come for even more precision in testing and targeted treatment of NSCLC. EGFR-mutated lung cancer is a perfect example of this need. The term "EGFR-positive lung cancer” is no longer adequate or specific enough to characterize this complex molecular subtype of lung cancer. Increased granularity is needed for both biomarker testing and targeted treatment selection for patients with different types of EGFR mutations. New agents and combinations have become available for patients with common (eg, exon 19 deletion, exon 21 L858R) and uncommon (eg, exon 20 insertions) EGFR mutations, and more are on the horizon. Novel strategies for overcoming resistance to EGFR-targeted therapies are showing great promise as well. This PeerView Live educational activity, based on a recent live symposium, explores the latest advances and future directions in biomarker-driven, individualized therapy for patients with NSCLC harboring common and less common EGFR mutations through engaging discussions and challenging case-based debates. Upon completion of this activity, participants should be better able to: Characterize the different types of EGFR mutations in NSCLC, their role as therapeutic targets, and evidence supporting the use of current and emerging targeted therapies or combinations for NSCLC with various common or uncommon EGFR mutations; Collaborate with the multidisciplinary team to promote widespread biomarker testing in patients with NSCLC, select appropriate tests to detect common and less common EGFR mutations, and ensure accurate interpretation of results to guide targeted therapy selection; and Apply current evidence and guidelines to individualize targeted therapy for patients with NSCLC exhibiting different EGFR mutations based on the efficacy and safety profile of the therapies, disease characteristics, and patient needs and preferences.

Go online to PeerView.com/DCG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The time has come for even more precision in testing and targeted treatment of NSCLC. EGFR-mutated lung cancer is a perfect example of this need. The term "EGFR-positive lung cancer” is no longer adequate or specific enough to characterize this complex molecular subtype of lung cancer. Increased granularity is needed for both biomarker testing and targeted treatment selection for patients with different types of EGFR mutations. New agents and combinations have become available for patients with common (eg, exon 19 deletion, exon 21 L858R) and uncommon (eg, exon 20 insertions) EGFR mutations, and more are on the horizon. Novel strategies for overcoming resistance to EGFR-targeted therapies are showing great promise as well. This PeerView Live educational activity, based on a recent live symposium, explores the latest advances and future directions in biomarker-driven, individualized therapy for patients with NSCLC harboring common and less common EGFR mutations through engaging discussions and challenging case-based debates. Upon completion of this activity, participants should be better able to: Characterize the different types of EGFR mutations in NSCLC, their role as therapeutic targets, and evidence supporting the use of current and emerging targeted therapies or combinations for NSCLC with various common or uncommon EGFR mutations; Collaborate with the multidisciplinary team to promote widespread biomarker testing in patients with NSCLC, select appropriate tests to detect common and less common EGFR mutations, and ensure accurate interpretation of results to guide targeted therapy selection; and Apply current evidence and guidelines to individualize targeted therapy for patients with NSCLC exhibiting different EGFR mutations based on the efficacy and safety profile of the therapies, disease characteristics, and patient needs and preferences.

Go online to PeerView.com/DCG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The time has come for even more precision in testing and targeted treatment of NSCLC. EGFR-mutated lung cancer is a perfect example of this need. The term "EGFR-positive lung cancer” is no longer adequate or specific enough to characterize this complex molecular subtype of lung cancer. Increased granularity is needed for both biomarker testing and targeted treatment selection for patients with different types of EGFR mutations. New agents and combinations have become available for patients with common (eg, exon 19 deletion, exon 21 L858R) and uncommon (eg, exon 20 insertions) EGFR mutations, and more are on the horizon. Novel strategies for overcoming resistance to EGFR-targeted therapies are showing great promise as well. This PeerView Live educational activity, based on a recent live symposium, explores the latest advances and future directions in biomarker-driven, individualized therapy for patients with NSCLC harboring common and less common EGFR mutations through engaging discussions and challenging case-based debates. Upon completion of this activity, participants should be better able to: Characterize the different types of EGFR mutations in NSCLC, their role as therapeutic targets, and evidence supporting the use of current and emerging targeted therapies or combinations for NSCLC with various common or uncommon EGFR mutations; Collaborate with the multidisciplinary team to promote widespread biomarker testing in patients with NSCLC, select appropriate tests to detect common and less common EGFR mutations, and ensure accurate interpretation of results to guide targeted therapy selection; and Apply current evidence and guidelines to individualize targeted therapy for patients with NSCLC exhibiting different EGFR mutations based on the efficacy and safety profile of the therapies, disease characteristics, and patient needs and preferences.

Go online to PeerView.com/GQW860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Patients with early-stage lung cancer frequently experience disease recurrence within 1 year of receiving curative-intent surgery, representing a significant unmet medical need. Individualized management of patients with NSCLC is based on a number of considerations, including the molecular profile of the patient's tumor and the benefits and limitations of therapeutic options in the context of the latest evidence. Continued advances with targeted therapies have sparked substantial interest in expanding their use into earlier disease settings, and adjuvant EGFR-targeted therapy has demonstrated remarkable efficacy in early-stage NSCLC, leading to the first regulatory approval of osimertinib as adjuvant therapy after resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. In addition, results from studies in the neoadjuvant setting are emerging now, as perioperative use of EGFR-targeted therapy continues to demonstrate improved outcomes. Thoracic surgeons are key members of the multidisciplinary care team, playing an essential role in collaborating and coordinating with other specialists to determine the best treatment plan, including incorporating EGFR-targeted therapy into multimodal management strategies. This PeerView educational activity, based on a recent live symposium, focuses on the latest clinical evidence supporting the use of EGFR-targeted therapy in perioperative settings and provides practical guidance for optimally integrating targeted therapies in practice or clinical trials. Multidisciplinary discussions on the latest practice-changing data highlight important implications of utilizing EGFR-targeted therapy as part of multimodal treatment for surgeons and the broader lung cancer care team. Upon completion of this activity, participants should be better able to: Discuss the role of EGFR mutations in NSCLC, advances in EGFR-targeted therapy in earlier disease settings, and the importance of identifying patients who might benefit from these therapies in perioperative settings; Identify patients with early-stage resectable NSCLC who are candidates for adjuvant EGFR-targeted therapy or investigational targeted approaches according to the latest evidence and guidelines; and Implement multidisciplinary and patient-centric strategies to integrate EGFR-targeted therapy into multimodal treatment plans for eligible patients with early-stage resectable NSCLC

Go online to PeerView.com/GQW860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Patients with early-stage lung cancer frequently experience disease recurrence within 1 year of receiving curative-intent surgery, representing a significant unmet medical need. Individualized management of patients with NSCLC is based on a number of considerations, including the molecular profile of the patient's tumor and the benefits and limitations of therapeutic options in the context of the latest evidence. Continued advances with targeted therapies have sparked substantial interest in expanding their use into earlier disease settings, and adjuvant EGFR-targeted therapy has demonstrated remarkable efficacy in early-stage NSCLC, leading to the first regulatory approval of osimertinib as adjuvant therapy after resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. In addition, results from studies in the neoadjuvant setting are emerging now, as perioperative use of EGFR-targeted therapy continues to demonstrate improved outcomes. Thoracic surgeons are key members of the multidisciplinary care team, playing an essential role in collaborating and coordinating with other specialists to determine the best treatment plan, including incorporating EGFR-targeted therapy into multimodal management strategies. This PeerView educational activity, based on a recent live symposium, focuses on the latest clinical evidence supporting the use of EGFR-targeted therapy in perioperative settings and provides practical guidance for optimally integrating targeted therapies in practice or clinical trials. Multidisciplinary discussions on the latest practice-changing data highlight important implications of utilizing EGFR-targeted therapy as part of multimodal treatment for surgeons and the broader lung cancer care team. Upon completion of this activity, participants should be better able to: Discuss the role of EGFR mutations in NSCLC, advances in EGFR-targeted therapy in earlier disease settings, and the importance of identifying patients who might benefit from these therapies in perioperative settings; Identify patients with early-stage resectable NSCLC who are candidates for adjuvant EGFR-targeted therapy or investigational targeted approaches according to the latest evidence and guidelines; and Implement multidisciplinary and patient-centric strategies to integrate EGFR-targeted therapy into multimodal treatment plans for eligible patients with early-stage resectable NSCLC

Go online to PeerView.com/GQW860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Patients with early-stage lung cancer frequently experience disease recurrence within 1 year of receiving curative-intent surgery, representing a significant unmet medical need. Individualized management of patients with NSCLC is based on a number of considerations, including the molecular profile of the patient's tumor and the benefits and limitations of therapeutic options in the context of the latest evidence. Continued advances with targeted therapies have sparked substantial interest in expanding their use into earlier disease settings, and adjuvant EGFR-targeted therapy has demonstrated remarkable efficacy in early-stage NSCLC, leading to the first regulatory approval of osimertinib as adjuvant therapy after resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. In addition, results from studies in the neoadjuvant setting are emerging now, as perioperative use of EGFR-targeted therapy continues to demonstrate improved outcomes. Thoracic surgeons are key members of the multidisciplinary care team, playing an essential role in collaborating and coordinating with other specialists to determine the best treatment plan, including incorporating EGFR-targeted therapy into multimodal management strategies. This PeerView educational activity, based on a recent live symposium, focuses on the latest clinical evidence supporting the use of EGFR-targeted therapy in perioperative settings and provides practical guidance for optimally integrating targeted therapies in practice or clinical trials. Multidisciplinary discussions on the latest practice-changing data highlight important implications of utilizing EGFR-targeted therapy as part of multimodal treatment for surgeons and the broader lung cancer care team. Upon completion of this activity, participants should be better able to: Discuss the role of EGFR mutations in NSCLC, advances in EGFR-targeted therapy in earlier disease settings, and the importance of identifying patients who might benefit from these therapies in perioperative settings; Identify patients with early-stage resectable NSCLC who are candidates for adjuvant EGFR-targeted therapy or investigational targeted approaches according to the latest evidence and guidelines; and Implement multidisciplinary and patient-centric strategies to integrate EGFR-targeted therapy into multimodal treatment plans for eligible patients with early-stage resectable NSCLC

Go online to PeerView.com/GQW860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Patients with early-stage lung cancer frequently experience disease recurrence within 1 year of receiving curative-intent surgery, representing a significant unmet medical need. Individualized management of patients with NSCLC is based on a number of considerations, including the molecular profile of the patient's tumor and the benefits and limitations of therapeutic options in the context of the latest evidence. Continued advances with targeted therapies have sparked substantial interest in expanding their use into earlier disease settings, and adjuvant EGFR-targeted therapy has demonstrated remarkable efficacy in early-stage NSCLC, leading to the first regulatory approval of osimertinib as adjuvant therapy after resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. In addition, results from studies in the neoadjuvant setting are emerging now, as perioperative use of EGFR-targeted therapy continues to demonstrate improved outcomes. Thoracic surgeons are key members of the multidisciplinary care team, playing an essential role in collaborating and coordinating with other specialists to determine the best treatment plan, including incorporating EGFR-targeted therapy into multimodal management strategies. This PeerView educational activity, based on a recent live symposium, focuses on the latest clinical evidence supporting the use of EGFR-targeted therapy in perioperative settings and provides practical guidance for optimally integrating targeted therapies in practice or clinical trials. Multidisciplinary discussions on the latest practice-changing data highlight important implications of utilizing EGFR-targeted therapy as part of multimodal treatment for surgeons and the broader lung cancer care team. Upon completion of this activity, participants should be better able to: Discuss the role of EGFR mutations in NSCLC, advances in EGFR-targeted therapy in earlier disease settings, and the importance of identifying patients who might benefit from these therapies in perioperative settings; Identify patients with early-stage resectable NSCLC who are candidates for adjuvant EGFR-targeted therapy or investigational targeted approaches according to the latest evidence and guidelines; and Implement multidisciplinary and patient-centric strategies to integrate EGFR-targeted therapy into multimodal treatment plans for eligible patients with early-stage resectable NSCLC

Go online to PeerView.com/GQW860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Patients with early-stage lung cancer frequently experience disease recurrence within 1 year of receiving curative-intent surgery, representing a significant unmet medical need. Individualized management of patients with NSCLC is based on a number of considerations, including the molecular profile of the patient's tumor and the benefits and limitations of therapeutic options in the context of the latest evidence. Continued advances with targeted therapies have sparked substantial interest in expanding their use into earlier disease settings, and adjuvant EGFR-targeted therapy has demonstrated remarkable efficacy in early-stage NSCLC, leading to the first regulatory approval of osimertinib as adjuvant therapy after resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. In addition, results from studies in the neoadjuvant setting are emerging now, as perioperative use of EGFR-targeted therapy continues to demonstrate improved outcomes. Thoracic surgeons are key members of the multidisciplinary care team, playing an essential role in collaborating and coordinating with other specialists to determine the best treatment plan, including incorporating EGFR-targeted therapy into multimodal management strategies. This PeerView educational activity, based on a recent live symposium, focuses on the latest clinical evidence supporting the use of EGFR-targeted therapy in perioperative settings and provides practical guidance for optimally integrating targeted therapies in practice or clinical trials. Multidisciplinary discussions on the latest practice-changing data highlight important implications of utilizing EGFR-targeted therapy as part of multimodal treatment for surgeons and the broader lung cancer care team. Upon completion of this activity, participants should be better able to: Discuss the role of EGFR mutations in NSCLC, advances in EGFR-targeted therapy in earlier disease settings, and the importance of identifying patients who might benefit from these therapies in perioperative settings; Identify patients with early-stage resectable NSCLC who are candidates for adjuvant EGFR-targeted therapy or investigational targeted approaches according to the latest evidence and guidelines; and Implement multidisciplinary and patient-centric strategies to integrate EGFR-targeted therapy into multimodal treatment plans for eligible patients with early-stage resectable NSCLC

Go online to PeerView.com/GQW860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Patients with early-stage lung cancer frequently experience disease recurrence within 1 year of receiving curative-intent surgery, representing a significant unmet medical need. Individualized management of patients with NSCLC is based on a number of considerations, including the molecular profile of the patient's tumor and the benefits and limitations of therapeutic options in the context of the latest evidence. Continued advances with targeted therapies have sparked substantial interest in expanding their use into earlier disease settings, and adjuvant EGFR-targeted therapy has demonstrated remarkable efficacy in early-stage NSCLC, leading to the first regulatory approval of osimertinib as adjuvant therapy after resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. In addition, results from studies in the neoadjuvant setting are emerging now, as perioperative use of EGFR-targeted therapy continues to demonstrate improved outcomes. Thoracic surgeons are key members of the multidisciplinary care team, playing an essential role in collaborating and coordinating with other specialists to determine the best treatment plan, including incorporating EGFR-targeted therapy into multimodal management strategies. This PeerView educational activity, based on a recent live symposium, focuses on the latest clinical evidence supporting the use of EGFR-targeted therapy in perioperative settings and provides practical guidance for optimally integrating targeted therapies in practice or clinical trials. Multidisciplinary discussions on the latest practice-changing data highlight important implications of utilizing EGFR-targeted therapy as part of multimodal treatment for surgeons and the broader lung cancer care team. Upon completion of this activity, participants should be better able to: Discuss the role of EGFR mutations in NSCLC, advances in EGFR-targeted therapy in earlier disease settings, and the importance of identifying patients who might benefit from these therapies in perioperative settings; Identify patients with early-stage resectable NSCLC who are candidates for adjuvant EGFR-targeted therapy or investigational targeted approaches according to the latest evidence and guidelines; and Implement multidisciplinary and patient-centric strategies to integrate EGFR-targeted therapy into multimodal treatment plans for eligible patients with early-stage resectable NSCLC

Go online to PeerView.com/GQW860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Patients with early-stage lung cancer frequently experience disease recurrence within 1 year of receiving curative-intent surgery, representing a significant unmet medical need. Individualized management of patients with NSCLC is based on a number of considerations, including the molecular profile of the patient's tumor and the benefits and limitations of therapeutic options in the context of the latest evidence. Continued advances with targeted therapies have sparked substantial interest in expanding their use into earlier disease settings, and adjuvant EGFR-targeted therapy has demonstrated remarkable efficacy in early-stage NSCLC, leading to the first regulatory approval of osimertinib as adjuvant therapy after resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. In addition, results from studies in the neoadjuvant setting are emerging now, as perioperative use of EGFR-targeted therapy continues to demonstrate improved outcomes. Thoracic surgeons are key members of the multidisciplinary care team, playing an essential role in collaborating and coordinating with other specialists to determine the best treatment plan, including incorporating EGFR-targeted therapy into multimodal management strategies. This PeerView educational activity, based on a recent live symposium, focuses on the latest clinical evidence supporting the use of EGFR-targeted therapy in perioperative settings and provides practical guidance for optimally integrating targeted therapies in practice or clinical trials. Multidisciplinary discussions on the latest practice-changing data highlight important implications of utilizing EGFR-targeted therapy as part of multimodal treatment for surgeons and the broader lung cancer care team. Upon completion of this activity, participants should be better able to: Discuss the role of EGFR mutations in NSCLC, advances in EGFR-targeted therapy in earlier disease settings, and the importance of identifying patients who might benefit from these therapies in perioperative settings; Identify patients with early-stage resectable NSCLC who are candidates for adjuvant EGFR-targeted therapy or investigational targeted approaches according to the latest evidence and guidelines; and Implement multidisciplinary and patient-centric strategies to integrate EGFR-targeted therapy into multimodal treatment plans for eligible patients with early-stage resectable NSCLC

Go online to PeerView.com/GQW860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Patients with early-stage lung cancer frequently experience disease recurrence within 1 year of receiving curative-intent surgery, representing a significant unmet medical need. Individualized management of patients with NSCLC is based on a number of considerations, including the molecular profile of the patient's tumor and the benefits and limitations of therapeutic options in the context of the latest evidence. Continued advances with targeted therapies have sparked substantial interest in expanding their use into earlier disease settings, and adjuvant EGFR-targeted therapy has demonstrated remarkable efficacy in early-stage NSCLC, leading to the first regulatory approval of osimertinib as adjuvant therapy after resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. In addition, results from studies in the neoadjuvant setting are emerging now, as perioperative use of EGFR-targeted therapy continues to demonstrate improved outcomes. Thoracic surgeons are key members of the multidisciplinary care team, playing an essential role in collaborating and coordinating with other specialists to determine the best treatment plan, including incorporating EGFR-targeted therapy into multimodal management strategies. This PeerView educational activity, based on a recent live symposium, focuses on the latest clinical evidence supporting the use of EGFR-targeted therapy in perioperative settings and provides practical guidance for optimally integrating targeted therapies in practice or clinical trials. Multidisciplinary discussions on the latest practice-changing data highlight important implications of utilizing EGFR-targeted therapy as part of multimodal treatment for surgeons and the broader lung cancer care team. Upon completion of this activity, participants should be better able to: Discuss the role of EGFR mutations in NSCLC, advances in EGFR-targeted therapy in earlier disease settings, and the importance of identifying patients who might benefit from these therapies in perioperative settings; Identify patients with early-stage resectable NSCLC who are candidates for adjuvant EGFR-targeted therapy or investigational targeted approaches according to the latest evidence and guidelines; and Implement multidisciplinary and patient-centric strategies to integrate EGFR-targeted therapy into multimodal treatment plans for eligible patients with early-stage resectable NSCLC

Go online to PeerView.com/RJV860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The term "EGFR-positive lung cancer” is no longer adequate or specific enough to characterize this complex molecular subtype of lung cancer. Increased granularity is needed both in biomarker testing and targeted treatment selection for patients with different types of EGFR mutations. A growing number of new agents and combinations have become available for patients with common (eg, exon 19 deletion, exon 21 L858R) and uncommon (eg, exon 20 insertions) EGFR mutations, and more are on the horizon, requiring a precision approach. Watch PeerView's latest educational video, based on a recent live symposium, and learn to better navigate biomarker-driven, individualized therapy for patients with EGFR-mutated NSCLC. Experts analyze the expanding evidence base and provide actionable, case-based guidance for improving testing, interpretation of results, and therapeutic decision-making for patients with NSCLC across a variety of EGFR mutations. Upon completion of this activity, participants should be better able to: Review the different types of EGFR mutations and their role as therapeutic targets in NSCLC, including in earlier disease stages; Collaborate with the multidisciplinary team to promote widespread biomarker testing in patients with NSCLC, select appropriate tests to detect common and less common EGFR mutations, and ensure accurate interpretation of results to guide targeted therapy selection; Apply current evidence and guidelines to individualize targeted therapy for patients with EGFR-mutated NSCLC based on EGFR mutation type and patient needs, values, and preferences; and Communicate with the multidisciplinary team and with patients to promote rapid detection and management of treatment-related adverse events in patients receiving EGFR-targeted therapies for NSCLC.

Go online to PeerView.com/RJV860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The term "EGFR-positive lung cancer” is no longer adequate or specific enough to characterize this complex molecular subtype of lung cancer. Increased granularity is needed both in biomarker testing and targeted treatment selection for patients with different types of EGFR mutations. A growing number of new agents and combinations have become available for patients with common (eg, exon 19 deletion, exon 21 L858R) and uncommon (eg, exon 20 insertions) EGFR mutations, and more are on the horizon, requiring a precision approach. Watch PeerView's latest educational video, based on a recent live symposium, and learn to better navigate biomarker-driven, individualized therapy for patients with EGFR-mutated NSCLC. Experts analyze the expanding evidence base and provide actionable, case-based guidance for improving testing, interpretation of results, and therapeutic decision-making for patients with NSCLC across a variety of EGFR mutations. Upon completion of this activity, participants should be better able to: Review the different types of EGFR mutations and their role as therapeutic targets in NSCLC, including in earlier disease stages; Collaborate with the multidisciplinary team to promote widespread biomarker testing in patients with NSCLC, select appropriate tests to detect common and less common EGFR mutations, and ensure accurate interpretation of results to guide targeted therapy selection; Apply current evidence and guidelines to individualize targeted therapy for patients with EGFR-mutated NSCLC based on EGFR mutation type and patient needs, values, and preferences; and Communicate with the multidisciplinary team and with patients to promote rapid detection and management of treatment-related adverse events in patients receiving EGFR-targeted therapies for NSCLC.

Go online to PeerView.com/RJV860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The term "EGFR-positive lung cancer” is no longer adequate or specific enough to characterize this complex molecular subtype of lung cancer. Increased granularity is needed both in biomarker testing and targeted treatment selection for patients with different types of EGFR mutations. A growing number of new agents and combinations have become available for patients with common (eg, exon 19 deletion, exon 21 L858R) and uncommon (eg, exon 20 insertions) EGFR mutations, and more are on the horizon, requiring a precision approach. Watch PeerView's latest educational video, based on a recent live symposium, and learn to better navigate biomarker-driven, individualized therapy for patients with EGFR-mutated NSCLC. Experts analyze the expanding evidence base and provide actionable, case-based guidance for improving testing, interpretation of results, and therapeutic decision-making for patients with NSCLC across a variety of EGFR mutations. Upon completion of this activity, participants should be better able to: Review the different types of EGFR mutations and their role as therapeutic targets in NSCLC, including in earlier disease stages; Collaborate with the multidisciplinary team to promote widespread biomarker testing in patients with NSCLC, select appropriate tests to detect common and less common EGFR mutations, and ensure accurate interpretation of results to guide targeted therapy selection; Apply current evidence and guidelines to individualize targeted therapy for patients with EGFR-mutated NSCLC based on EGFR mutation type and patient needs, values, and preferences; and Communicate with the multidisciplinary team and with patients to promote rapid detection and management of treatment-related adverse events in patients receiving EGFR-targeted therapies for NSCLC.

Go online to PeerView.com/RJV860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The term "EGFR-positive lung cancer” is no longer adequate or specific enough to characterize this complex molecular subtype of lung cancer. Increased granularity is needed both in biomarker testing and targeted treatment selection for patients with different types of EGFR mutations. A growing number of new agents and combinations have become available for patients with common (eg, exon 19 deletion, exon 21 L858R) and uncommon (eg, exon 20 insertions) EGFR mutations, and more are on the horizon, requiring a precision approach. Watch PeerView's latest educational video, based on a recent live symposium, and learn to better navigate biomarker-driven, individualized therapy for patients with EGFR-mutated NSCLC. Experts analyze the expanding evidence base and provide actionable, case-based guidance for improving testing, interpretation of results, and therapeutic decision-making for patients with NSCLC across a variety of EGFR mutations. Upon completion of this activity, participants should be better able to: Review the different types of EGFR mutations and their role as therapeutic targets in NSCLC, including in earlier disease stages; Collaborate with the multidisciplinary team to promote widespread biomarker testing in patients with NSCLC, select appropriate tests to detect common and less common EGFR mutations, and ensure accurate interpretation of results to guide targeted therapy selection; Apply current evidence and guidelines to individualize targeted therapy for patients with EGFR-mutated NSCLC based on EGFR mutation type and patient needs, values, and preferences; and Communicate with the multidisciplinary team and with patients to promote rapid detection and management of treatment-related adverse events in patients receiving EGFR-targeted therapies for NSCLC.

Go online to PeerView.com/RJV860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The term "EGFR-positive lung cancer” is no longer adequate or specific enough to characterize this complex molecular subtype of lung cancer. Increased granularity is needed both in biomarker testing and targeted treatment selection for patients with different types of EGFR mutations. A growing number of new agents and combinations have become available for patients with common (eg, exon 19 deletion, exon 21 L858R) and uncommon (eg, exon 20 insertions) EGFR mutations, and more are on the horizon, requiring a precision approach. Watch PeerView's latest educational video, based on a recent live symposium, and learn to better navigate biomarker-driven, individualized therapy for patients with EGFR-mutated NSCLC. Experts analyze the expanding evidence base and provide actionable, case-based guidance for improving testing, interpretation of results, and therapeutic decision-making for patients with NSCLC across a variety of EGFR mutations. Upon completion of this activity, participants should be better able to: Review the different types of EGFR mutations and their role as therapeutic targets in NSCLC, including in earlier disease stages; Collaborate with the multidisciplinary team to promote widespread biomarker testing in patients with NSCLC, select appropriate tests to detect common and less common EGFR mutations, and ensure accurate interpretation of results to guide targeted therapy selection; Apply current evidence and guidelines to individualize targeted therapy for patients with EGFR-mutated NSCLC based on EGFR mutation type and patient needs, values, and preferences; and Communicate with the multidisciplinary team and with patients to promote rapid detection and management of treatment-related adverse events in patients receiving EGFR-targeted therapies for NSCLC.

Go online to PeerView.com/RJV860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The term "EGFR-positive lung cancer” is no longer adequate or specific enough to characterize this complex molecular subtype of lung cancer. Increased granularity is needed both in biomarker testing and targeted treatment selection for patients with different types of EGFR mutations. A growing number of new agents and combinations have become available for patients with common (eg, exon 19 deletion, exon 21 L858R) and uncommon (eg, exon 20 insertions) EGFR mutations, and more are on the horizon, requiring a precision approach. Watch PeerView's latest educational video, based on a recent live symposium, and learn to better navigate biomarker-driven, individualized therapy for patients with EGFR-mutated NSCLC. Experts analyze the expanding evidence base and provide actionable, case-based guidance for improving testing, interpretation of results, and therapeutic decision-making for patients with NSCLC across a variety of EGFR mutations. Upon completion of this activity, participants should be better able to: Review the different types of EGFR mutations and their role as therapeutic targets in NSCLC, including in earlier disease stages; Collaborate with the multidisciplinary team to promote widespread biomarker testing in patients with NSCLC, select appropriate tests to detect common and less common EGFR mutations, and ensure accurate interpretation of results to guide targeted therapy selection; Apply current evidence and guidelines to individualize targeted therapy for patients with EGFR-mutated NSCLC based on EGFR mutation type and patient needs, values, and preferences; and Communicate with the multidisciplinary team and with patients to promote rapid detection and management of treatment-related adverse events in patients receiving EGFR-targeted therapies for NSCLC.

Go online to PeerView.com/RJV860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The term "EGFR-positive lung cancer” is no longer adequate or specific enough to characterize this complex molecular subtype of lung cancer. Increased granularity is needed both in biomarker testing and targeted treatment selection for patients with different types of EGFR mutations. A growing number of new agents and combinations have become available for patients with common (eg, exon 19 deletion, exon 21 L858R) and uncommon (eg, exon 20 insertions) EGFR mutations, and more are on the horizon, requiring a precision approach. Watch PeerView's latest educational video, based on a recent live symposium, and learn to better navigate biomarker-driven, individualized therapy for patients with EGFR-mutated NSCLC. Experts analyze the expanding evidence base and provide actionable, case-based guidance for improving testing, interpretation of results, and therapeutic decision-making for patients with NSCLC across a variety of EGFR mutations. Upon completion of this activity, participants should be better able to: Review the different types of EGFR mutations and their role as therapeutic targets in NSCLC, including in earlier disease stages; Collaborate with the multidisciplinary team to promote widespread biomarker testing in patients with NSCLC, select appropriate tests to detect common and less common EGFR mutations, and ensure accurate interpretation of results to guide targeted therapy selection; Apply current evidence and guidelines to individualize targeted therapy for patients with EGFR-mutated NSCLC based on EGFR mutation type and patient needs, values, and preferences; and Communicate with the multidisciplinary team and with patients to promote rapid detection and management of treatment-related adverse events in patients receiving EGFR-targeted therapies for NSCLC.

Go online to PeerView.com/RJV860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The term "EGFR-positive lung cancer” is no longer adequate or specific enough to characterize this complex molecular subtype of lung cancer. Increased granularity is needed both in biomarker testing and targeted treatment selection for patients with different types of EGFR mutations. A growing number of new agents and combinations have become available for patients with common (eg, exon 19 deletion, exon 21 L858R) and uncommon (eg, exon 20 insertions) EGFR mutations, and more are on the horizon, requiring a precision approach. Watch PeerView's latest educational video, based on a recent live symposium, and learn to better navigate biomarker-driven, individualized therapy for patients with EGFR-mutated NSCLC. Experts analyze the expanding evidence base and provide actionable, case-based guidance for improving testing, interpretation of results, and therapeutic decision-making for patients with NSCLC across a variety of EGFR mutations. Upon completion of this activity, participants should be better able to: Review the different types of EGFR mutations and their role as therapeutic targets in NSCLC, including in earlier disease stages; Collaborate with the multidisciplinary team to promote widespread biomarker testing in patients with NSCLC, select appropriate tests to detect common and less common EGFR mutations, and ensure accurate interpretation of results to guide targeted therapy selection; Apply current evidence and guidelines to individualize targeted therapy for patients with EGFR-mutated NSCLC based on EGFR mutation type and patient needs, values, and preferences; and Communicate with the multidisciplinary team and with patients to promote rapid detection and management of treatment-related adverse events in patients receiving EGFR-targeted therapies for NSCLC.

Go online to PeerView.com/WRG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Approximately 40% of patients with early-stage lung cancer experience disease recurrence within 1 year of receiving curative-intent surgery, representing a significant unmet medical need. Management of patients with NSCLC should be individualized based on a number of factors, including the molecular profile of the patient's tumor and the benefits and limitations of therapeutic options in the context of the latest evidence. Continued advances with targeted therapies have prompted strong interest in expanding their use into earlier disease settings, and adjuvant EGFR-targeted therapy has demonstrated remarkable efficacy in early-stage NSCLC, leading to the first regulatory approval of osimertinib as adjuvant therapy after resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. Early findings from studies in the neoadjuvant setting are beginning to emerge now as well, as perioperative use of EGFR-targeted therapy continues to demonstrate improved outcomes. As part of the multidisciplinary team, thoracic surgeons play an essential role in collaborating and coordinating with other specialists to determine the best treatment plan, including incorporating EGFR-targeted therapy into multimodal management strategies. This PeerView educational video, based on a recent live symposium, provides an essential overview of the latest clinical evidence supporting the use of EGFR-targeted therapy in perioperative settings, as well as practical advice for optimal integration of targeted therapies in practice or as part of a clinical trial. Multidisciplinary discussions on the new practice-changing data highlight important implications for the surgeon–oncologist partnership, utilizing EGFR-targeted therapy as part of multimodal management of patients with resectable NSCLC with the goal of improving outcomes and quality of life. Upon completion of this activity, participants should be better able to: Review the role of EGFR mutations in NSCLC, advances in EGFR-targeted therapy in earlier disease settings, and importance of identifying patients who might benefit from these therapies in perioperative settings; Apply the latest evidence and guidelines to identify patients with early-stage resectable NSCLC who are candidates for adjuvant EGFR-targeted therapy or investigational targeted approaches; Collaborate with the multidisciplinary team to integrate EGFR-targeted therapy into multimodal treatment plans for eligible patients with early-stage resectable NSCLC

Go online to PeerView.com/WRG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Approximately 40% of patients with early-stage lung cancer experience disease recurrence within 1 year of receiving curative-intent surgery, representing a significant unmet medical need. Management of patients with NSCLC should be individualized based on a number of factors, including the molecular profile of the patient's tumor and the benefits and limitations of therapeutic options in the context of the latest evidence. Continued advances with targeted therapies have prompted strong interest in expanding their use into earlier disease settings, and adjuvant EGFR-targeted therapy has demonstrated remarkable efficacy in early-stage NSCLC, leading to the first regulatory approval of osimertinib as adjuvant therapy after resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. Early findings from studies in the neoadjuvant setting are beginning to emerge now as well, as perioperative use of EGFR-targeted therapy continues to demonstrate improved outcomes. As part of the multidisciplinary team, thoracic surgeons play an essential role in collaborating and coordinating with other specialists to determine the best treatment plan, including incorporating EGFR-targeted therapy into multimodal management strategies. This PeerView educational video, based on a recent live symposium, provides an essential overview of the latest clinical evidence supporting the use of EGFR-targeted therapy in perioperative settings, as well as practical advice for optimal integration of targeted therapies in practice or as part of a clinical trial. Multidisciplinary discussions on the new practice-changing data highlight important implications for the surgeon–oncologist partnership, utilizing EGFR-targeted therapy as part of multimodal management of patients with resectable NSCLC with the goal of improving outcomes and quality of life. Upon completion of this activity, participants should be better able to: Review the role of EGFR mutations in NSCLC, advances in EGFR-targeted therapy in earlier disease settings, and importance of identifying patients who might benefit from these therapies in perioperative settings; Apply the latest evidence and guidelines to identify patients with early-stage resectable NSCLC who are candidates for adjuvant EGFR-targeted therapy or investigational targeted approaches; Collaborate with the multidisciplinary team to integrate EGFR-targeted therapy into multimodal treatment plans for eligible patients with early-stage resectable NSCLC

Go online to PeerView.com/WRG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Approximately 40% of patients with early-stage lung cancer experience disease recurrence within 1 year of receiving curative-intent surgery, representing a significant unmet medical need. Management of patients with NSCLC should be individualized based on a number of factors, including the molecular profile of the patient's tumor and the benefits and limitations of therapeutic options in the context of the latest evidence. Continued advances with targeted therapies have prompted strong interest in expanding their use into earlier disease settings, and adjuvant EGFR-targeted therapy has demonstrated remarkable efficacy in early-stage NSCLC, leading to the first regulatory approval of osimertinib as adjuvant therapy after resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. Early findings from studies in the neoadjuvant setting are beginning to emerge now as well, as perioperative use of EGFR-targeted therapy continues to demonstrate improved outcomes. As part of the multidisciplinary team, thoracic surgeons play an essential role in collaborating and coordinating with other specialists to determine the best treatment plan, including incorporating EGFR-targeted therapy into multimodal management strategies. This PeerView educational video, based on a recent live symposium, provides an essential overview of the latest clinical evidence supporting the use of EGFR-targeted therapy in perioperative settings, as well as practical advice for optimal integration of targeted therapies in practice or as part of a clinical trial. Multidisciplinary discussions on the new practice-changing data highlight important implications for the surgeon–oncologist partnership, utilizing EGFR-targeted therapy as part of multimodal management of patients with resectable NSCLC with the goal of improving outcomes and quality of life. Upon completion of this activity, participants should be better able to: Review the role of EGFR mutations in NSCLC, advances in EGFR-targeted therapy in earlier disease settings, and importance of identifying patients who might benefit from these therapies in perioperative settings; Apply the latest evidence and guidelines to identify patients with early-stage resectable NSCLC who are candidates for adjuvant EGFR-targeted therapy or investigational targeted approaches; Collaborate with the multidisciplinary team to integrate EGFR-targeted therapy into multimodal treatment plans for eligible patients with early-stage resectable NSCLC

Go online to PeerView.com/WRG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Approximately 40% of patients with early-stage lung cancer experience disease recurrence within 1 year of receiving curative-intent surgery, representing a significant unmet medical need. Management of patients with NSCLC should be individualized based on a number of factors, including the molecular profile of the patient's tumor and the benefits and limitations of therapeutic options in the context of the latest evidence. Continued advances with targeted therapies have prompted strong interest in expanding their use into earlier disease settings, and adjuvant EGFR-targeted therapy has demonstrated remarkable efficacy in early-stage NSCLC, leading to the first regulatory approval of osimertinib as adjuvant therapy after resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. Early findings from studies in the neoadjuvant setting are beginning to emerge now as well, as perioperative use of EGFR-targeted therapy continues to demonstrate improved outcomes. As part of the multidisciplinary team, thoracic surgeons play an essential role in collaborating and coordinating with other specialists to determine the best treatment plan, including incorporating EGFR-targeted therapy into multimodal management strategies. This PeerView educational video, based on a recent live symposium, provides an essential overview of the latest clinical evidence supporting the use of EGFR-targeted therapy in perioperative settings, as well as practical advice for optimal integration of targeted therapies in practice or as part of a clinical trial. Multidisciplinary discussions on the new practice-changing data highlight important implications for the surgeon–oncologist partnership, utilizing EGFR-targeted therapy as part of multimodal management of patients with resectable NSCLC with the goal of improving outcomes and quality of life. Upon completion of this activity, participants should be better able to: Review the role of EGFR mutations in NSCLC, advances in EGFR-targeted therapy in earlier disease settings, and importance of identifying patients who might benefit from these therapies in perioperative settings; Apply the latest evidence and guidelines to identify patients with early-stage resectable NSCLC who are candidates for adjuvant EGFR-targeted therapy or investigational targeted approaches; Collaborate with the multidisciplinary team to integrate EGFR-targeted therapy into multimodal treatment plans for eligible patients with early-stage resectable NSCLC

Go online to PeerView.com/WRG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Approximately 40% of patients with early-stage lung cancer experience disease recurrence within 1 year of receiving curative-intent surgery, representing a significant unmet medical need. Management of patients with NSCLC should be individualized based on a number of factors, including the molecular profile of the patient's tumor and the benefits and limitations of therapeutic options in the context of the latest evidence. Continued advances with targeted therapies have prompted strong interest in expanding their use into earlier disease settings, and adjuvant EGFR-targeted therapy has demonstrated remarkable efficacy in early-stage NSCLC, leading to the first regulatory approval of osimertinib as adjuvant therapy after resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. Early findings from studies in the neoadjuvant setting are beginning to emerge now as well, as perioperative use of EGFR-targeted therapy continues to demonstrate improved outcomes. As part of the multidisciplinary team, thoracic surgeons play an essential role in collaborating and coordinating with other specialists to determine the best treatment plan, including incorporating EGFR-targeted therapy into multimodal management strategies. This PeerView educational video, based on a recent live symposium, provides an essential overview of the latest clinical evidence supporting the use of EGFR-targeted therapy in perioperative settings, as well as practical advice for optimal integration of targeted therapies in practice or as part of a clinical trial. Multidisciplinary discussions on the new practice-changing data highlight important implications for the surgeon–oncologist partnership, utilizing EGFR-targeted therapy as part of multimodal management of patients with resectable NSCLC with the goal of improving outcomes and quality of life. Upon completion of this activity, participants should be better able to: Review the role of EGFR mutations in NSCLC, advances in EGFR-targeted therapy in earlier disease settings, and importance of identifying patients who might benefit from these therapies in perioperative settings; Apply the latest evidence and guidelines to identify patients with early-stage resectable NSCLC who are candidates for adjuvant EGFR-targeted therapy or investigational targeted approaches; Collaborate with the multidisciplinary team to integrate EGFR-targeted therapy into multimodal treatment plans for eligible patients with early-stage resectable NSCLC

Go online to PeerView.com/WRG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Approximately 40% of patients with early-stage lung cancer experience disease recurrence within 1 year of receiving curative-intent surgery, representing a significant unmet medical need. Management of patients with NSCLC should be individualized based on a number of factors, including the molecular profile of the patient's tumor and the benefits and limitations of therapeutic options in the context of the latest evidence. Continued advances with targeted therapies have prompted strong interest in expanding their use into earlier disease settings, and adjuvant EGFR-targeted therapy has demonstrated remarkable efficacy in early-stage NSCLC, leading to the first regulatory approval of osimertinib as adjuvant therapy after resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. Early findings from studies in the neoadjuvant setting are beginning to emerge now as well, as perioperative use of EGFR-targeted therapy continues to demonstrate improved outcomes. As part of the multidisciplinary team, thoracic surgeons play an essential role in collaborating and coordinating with other specialists to determine the best treatment plan, including incorporating EGFR-targeted therapy into multimodal management strategies. This PeerView educational video, based on a recent live symposium, provides an essential overview of the latest clinical evidence supporting the use of EGFR-targeted therapy in perioperative settings, as well as practical advice for optimal integration of targeted therapies in practice or as part of a clinical trial. Multidisciplinary discussions on the new practice-changing data highlight important implications for the surgeon–oncologist partnership, utilizing EGFR-targeted therapy as part of multimodal management of patients with resectable NSCLC with the goal of improving outcomes and quality of life. Upon completion of this activity, participants should be better able to: Review the role of EGFR mutations in NSCLC, advances in EGFR-targeted therapy in earlier disease settings, and importance of identifying patients who might benefit from these therapies in perioperative settings; Apply the latest evidence and guidelines to identify patients with early-stage resectable NSCLC who are candidates for adjuvant EGFR-targeted therapy or investigational targeted approaches; Collaborate with the multidisciplinary team to integrate EGFR-targeted therapy into multimodal treatment plans for eligible patients with early-stage resectable NSCLC

Go online to PeerView.com/WRG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Approximately 40% of patients with early-stage lung cancer experience disease recurrence within 1 year of receiving curative-intent surgery, representing a significant unmet medical need. Management of patients with NSCLC should be individualized based on a number of factors, including the molecular profile of the patient's tumor and the benefits and limitations of therapeutic options in the context of the latest evidence. Continued advances with targeted therapies have prompted strong interest in expanding their use into earlier disease settings, and adjuvant EGFR-targeted therapy has demonstrated remarkable efficacy in early-stage NSCLC, leading to the first regulatory approval of osimertinib as adjuvant therapy after resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. Early findings from studies in the neoadjuvant setting are beginning to emerge now as well, as perioperative use of EGFR-targeted therapy continues to demonstrate improved outcomes. As part of the multidisciplinary team, thoracic surgeons play an essential role in collaborating and coordinating with other specialists to determine the best treatment plan, including incorporating EGFR-targeted therapy into multimodal management strategies. This PeerView educational video, based on a recent live symposium, provides an essential overview of the latest clinical evidence supporting the use of EGFR-targeted therapy in perioperative settings, as well as practical advice for optimal integration of targeted therapies in practice or as part of a clinical trial. Multidisciplinary discussions on the new practice-changing data highlight important implications for the surgeon–oncologist partnership, utilizing EGFR-targeted therapy as part of multimodal management of patients with resectable NSCLC with the goal of improving outcomes and quality of life. Upon completion of this activity, participants should be better able to: Review the role of EGFR mutations in NSCLC, advances in EGFR-targeted therapy in earlier disease settings, and importance of identifying patients who might benefit from these therapies in perioperative settings; Apply the latest evidence and guidelines to identify patients with early-stage resectable NSCLC who are candidates for adjuvant EGFR-targeted therapy or investigational targeted approaches; Collaborate with the multidisciplinary team to integrate EGFR-targeted therapy into multimodal treatment plans for eligible patients with early-stage resectable NSCLC

Go online to PeerView.com/WRG860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Approximately 40% of patients with early-stage lung cancer experience disease recurrence within 1 year of receiving curative-intent surgery, representing a significant unmet medical need. Management of patients with NSCLC should be individualized based on a number of factors, including the molecular profile of the patient's tumor and the benefits and limitations of therapeutic options in the context of the latest evidence. Continued advances with targeted therapies have prompted strong interest in expanding their use into earlier disease settings, and adjuvant EGFR-targeted therapy has demonstrated remarkable efficacy in early-stage NSCLC, leading to the first regulatory approval of osimertinib as adjuvant therapy after resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. Early findings from studies in the neoadjuvant setting are beginning to emerge now as well, as perioperative use of EGFR-targeted therapy continues to demonstrate improved outcomes. As part of the multidisciplinary team, thoracic surgeons play an essential role in collaborating and coordinating with other specialists to determine the best treatment plan, including incorporating EGFR-targeted therapy into multimodal management strategies. This PeerView educational video, based on a recent live symposium, provides an essential overview of the latest clinical evidence supporting the use of EGFR-targeted therapy in perioperative settings, as well as practical advice for optimal integration of targeted therapies in practice or as part of a clinical trial. Multidisciplinary discussions on the new practice-changing data highlight important implications for the surgeon–oncologist partnership, utilizing EGFR-targeted therapy as part of multimodal management of patients with resectable NSCLC with the goal of improving outcomes and quality of life. Upon completion of this activity, participants should be better able to: Review the role of EGFR mutations in NSCLC, advances in EGFR-targeted therapy in earlier disease settings, and importance of identifying patients who might benefit from these therapies in perioperative settings; Apply the latest evidence and guidelines to identify patients with early-stage resectable NSCLC who are candidates for adjuvant EGFR-targeted therapy or investigational targeted approaches; Collaborate with the multidisciplinary team to integrate EGFR-targeted therapy into multimodal treatment plans for eligible patients with early-stage resectable NSCLC

In this episode, Ryan D. Gentzler, MD, MS, and Jonathan Riess, MD, MS, answer audience questions on managing EGFR-mutated non-small-cell lung cancer (NSCLC) from a live meeting series. The episode includes expert insights on:• Identifying patients who may benefit the most from adjuvant osimertinib  • Testing for EGFR mutations in early-stage NSCLC• Critical importance of getting molecular test results before starting immunotherapy• Monitoring cardiac toxicity in patients receiving osimertinib• Key ongoing trials in EGFR-mutated NSCLC for patients with newly diagnosed disease and following progression on osimertinibPresenters:Ryan D. Gentzler, MD, MSAssociate ProfessorDivision of Hematology/OncologyDepartment of MedicineUniversity of VirginiaThoracic Medical OncologistUniversity of Virginia Comprehensive Cancer CenterCharlottesville, VirginiaJonathan Riess, MD, MSAssociate ProfessorDepartment of Internal Medicine/Hematology-OncologyUniversity of California, DavisMedical Director, Thoracic OncologyUniversity of California, Davis Comprehensive Cancer CenterSacramento, CaliforniaLink to full program: https://bit.ly/3DZGzSO  

How do we think about treatment of lung cancer? Recap on staging (see Episode 025) * Pro-tip: Highly recommend that you “forget” about the actual staging and focus more on the individual T, N, and M status * Tumor size:**T1a

An interview with Dr. Megan Daly from University of California in Davis, California and Dr. Navneet Singh from the Postgraduate Institute of Medical Education & Research in Chandigarh, India, co-chairs on “Management of Stage III Non–Small-Cell Lung Cancer: ASCO Guideline.” They summarize guideline recommendations on five subtopics – evaluation & staging, surgery, neoadjuvant therapy, adjuvant therapy, and unresectable disease. Read the full guideline at www.asco.org/thoracic-cancer-guidelines.   TRANSCRIPT [MUSIC PLAYING]   ANNOUNCER: 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. BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at ASCO.org/podcasts. My name is Brittany Harvey, and today, I'm interviewing Dr. Megan Daley from University of California in Davis, California, and Dr. Navneet Singh from the Post-Graduate Institute of Medical Education and Research in Chandigarh, India, co-chairs on management of stage III non-small cell lung cancer ASCO guideline. Thank you for being here, Dr. Daley and Dr. Singh. MEGAN DALEY: Thank you for having us. NAVNEET SINGH: Thank you for having us, too. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Daley, do you have any relevant disclosures that are directly related to this guideline topic? MEGAN DALEY: I have research funding from EMD Serono, Merck, and Genentech. BRITTANY HARVEY: Thank you for those disclosures. Then Dr. Singh, do you have any relevant disclosures that are directly related to this guideline? NAVNEET SINGH: No, I have no financial conflicts of interest. BRITTANY HARVEY: Thank you. Getting into the content of this guideline, Dr. Singh, can you give us an overview of both the scope and the purpose of this guideline? NAVNEET SINGH: Yes, absolutely. So this guideline has been developed to assist clinicians involved in the management of patients with stage III non-small-cell lung cancer, or NSCLC, as we call it briefly. Now, stage III NSCLC represents one of the most heterogeneous subgroups of lung cancer. Consequently, it is also the subgroup in which the choice of multimodality treatment and the sequence of multimodality treatment varies significantly amongst clinicians, with variations being observed across institutes, as well as within an institute. And we sincerely hope that, with the help of this guideline, clinicians can accurately confirm the presence of stage III disease and offer the most appropriate treatment based on clinical and radiographic characteristics, as well as other medical factors that influence treatment decision-making. This evidence-based guidance also seeks to provide clarification on the common clinical dilemmas that clinicians may have while evaluating a patient with suspected or known stage III NSCLC. BRITTANY HARVEY: Thank you for that background information, Dr. Singh. Then, Dr. Daley, this guideline addresses five main sections, evaluation and staging, surgery, neoadjuvant therapy, adjuvant therapy, and unresectable disease. So starting with evaluation and staging, what are the key recommendations for workup for patients with suspected stage III non-small cell lung cancer? MEGAN DALEY: Our first recommendation for such patients is that they should undergo a history and physical exam and a CT scan of the chest and upper abdomen with contrast, unless it's contraindicated. If metastatic disease is not identified on CT, those patients should go on to a PET CT scan and MRI of the brain. If the patients are being considered for curative intent treatment, the guideline recommends pathologic mediastinal lymph node assessment. And we recommend that endoscopic techniques should be offered as the initial staging modality, if available. If not available, invasive surgical mediastinal staging should be offered. And finally, for patients who have suspected or confirmed stage III lung cancer, we recommend that multidisciplinary discussion should occur prior to any initiation of a treatment plan. BRITTANY HARVEY: Great, I appreciate your reviewing those recommendations. So following that, Dr. Singh, what does the guideline recommend regarding which patients with stage III non-small-cell lung cancer should be considered for surgical resection? NAVNEET SINGH: So in this guideline, the recommendation which has come forth is that for patients with stage IIIA, basically N2 disease, induction therapy should be followed by surgery with or without adjuvant therapy if several conditions are met. Basically, a complete resection of the primary tumor and the involved lymph nodes is deemed feasible, and three nodes or contralateral lymph nodes are deemed to be not involved, and the expected perioperative 90-day mortality is low, typically 5% or less. Another recommendation is that for selected patients with the P4N0 disease, surgical resection may be offered if medically and surgically feasible following multidisciplinary review. We would like to emphasize here that surgeons should always be involved in decisions regarding the feasibility of surgical resection. And they are an integral part of a multidisciplinary evaluation for surgical resection for stage III NSCLC patients. BRITTANY HARVEY: Great. Then Dr. Singh just reviewed who should be considered for surgical resection. So Dr. Daley, for patients with potentially resectable stage III non-small-cell lung cancer, what are the key recommendations for neoadjuvant therapy? MEGAN DALEY: Our first recommendation is that patients who are planned for a multimodality approach that will incorporate surgery should receive systemic neoadjuvant therapy. Second, that those patients with N2 disease who are planned for surgical resection should receive either neoadjuvant chemotherapy or neoadjuvant concurrent chemoradiation. And finally, for patients with a resectable superior sulcus tumor, neoadjuvant concurrent chemoradiation should be administered. BRITTANY HARVEY: Understood. Then in addition, Dr. Singh, for patients with resected stage III non-small-cell lung cancer, what are the key recommendations for adjuvant therapy? NAVNEET SINGH: So the panel came up with three recommendations for adjuvant treatment. The first is that patients with resected stage III NSCLC who did not receive neoadjuvant systemic therapy should be offered adjuvant platinum-based chemotherapy. The second recommendation which we came up was that for patients with resected stage III disease and presence of a sensitizing EGFR mutation-- classically, exon 19 deletion or the L858R exon 21 point mutation-- they may be offered adjuvant osimertinib, which is an EGFR inhibitor, after platinum-based chemotherapy. And this is based upon the ADAURA trial, which was published last year. And the third recommendation was that for patients with completely resected NSCLC and mediastinal involvement N2 disease, but without extracapsular extension, post-operative radiotherapy should not be routinely offered. BRITTANY HARVEY: OK. And then the last section of recommendations covers unresectable disease. So Dr. Daley, what does the guideline recommend regarding the management of unresectable stage III non-small-cell lung cancer? MEGAN DALEY: The guideline first recommends that these patients who have a good performance status should be offered concurrent, rather than sequential, chemoradiation, that concurrent chemotherapy delivered with radiation should include a platinum-based doublet, preferably cisplatin-etoposide, carboplatin-paclitaxel, or cisplatin-pemetrexed or cisplatin-vinorelbine. The patients who are not candidates for concurrent chemoradiation, but who are potentially candidates for chemotherapy, should be offered sequential chemoradiation, rather than radiation alone, that patients receiving concurrent chemoradiation should be treated to 60 gray. And that's based on the results of RTOG 0617. We also recommend within the guideline that doses higher than 60 gray and up to 70 gray could be considered for selected patients, with careful attention to doses to the heart, lung, and esophagus, among other organs. The guideline also recommends that patients receiving definitive radiation without chemotherapy, that hypofractionation using slightly larger doses could be considered-- over 2 gray per fraction, and up to 4 gray per fraction, and that patients without disease progression during concurrent chemoradiation should be offered consolidation durvalumab, based on the PACIFIC trial. BRITTANY HARVEY: Thank you both, then, for reviewing the key recommendations of this guideline. So, Dr. Singh, in your view, what is the importance of this guideline, and how does it impact clinicians? NAVNEET SINGH: I think this guideline will go a long way in helping clinicians who are involved in the diagnosis and treatment of lung cancer, especially stage III NSCLC. As mentioned earlier, this is a very heterogeneous disease. And there are several challenging situations, both in the context of diagnosis, as well as treatment. And using this guideline, which has an extensive evidence review, as well as the development of two very helpful algorithms, we sincerely hope that clinicians who are both in academic centers as well as in practice in the community are able to accurately diagnose stage III, appropriately stage it, and offer the best treatment, given the patient characteristics and the disease characteristics and available resources. BRITTANY HARVEY: Great. Those are important points. So then, finally, Dr. Daley, how will these guideline recommendations affect patients? MEGAN DALEY: Well, we hope very much that these guidelines will help patients consistently receive high-quality care for their stage III lung cancer. In particular, we're hoping that the recommendation from multidisciplinary assessment of patients prior to treatment is carefully followed. We're hoping that some of the recommendations surrounding the appropriate workup for patients may help ensure that all patients receive a thorough and complete workup prior to initiation of treatment. And the guideline, in particular, is highlighting some of the more recent developments in stage III lung cancer, such as the use of consolidation durvalumab based on the PACIFIC trial, the use of osimertinib in resectable disease based on the ADAURA trial. And we're hoping to make sure that these results are disseminated to practitioners everywhere so that patients can receive the latest and best care for their stage III lung cancer. BRITTANY HARVEY: Understood. Yeah, as you both mentioned, we hope that this has a positive impact for both clinicians and patients. So I want to thank you both for all of your hard work to develop this guideline and the evidence-based recommendations along with it. And thank you for taking the time to speak with me today, Dr. Daley and Dr. Singh. MEGAN DALEY: Thank you so much for having us. NAVNEET SINGH: Thank you. BRITTANY HARVEY: And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app, available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

El Dr. Eleazar Omar Macedo Pérez, oncólogo médico adscrito al Instituto Nacional de Cancerología en la Ciudad de México, México, junto a la Dra. Tannia Soria Samaniego, oncóloga clínica del Hospital de Solca en Quito, Ecuador, nos comentan sobre lo más destacado en cáncer de pulmón presentado en ASCO 2021, resaltando los siguientes estudios: Enfermedad temprana: IMpowe010: Estudio fase lll, donde se demuestra que atezolizumab retrasa la recurrencia y prolonga la supervivencia libre de enfermedad en pacientes con cáncer de pulmón de células no pequeñas (CPCNP) en estadio temprano resecado. CheckMate 816: Estudio fase lll, con quimioterapia neoadyuvante en donde se compara nivolumab + quimioterapia por 3 ciclos vs. quimioterapia neoadyuvante. NEJ009: Estudio donde se compara gefitinib + quimioterapia adyuvante vs. gefitinib como monoterapia en pacientes con mutación de EGFR en etapas II y IIIA resecados, demostrando una mejora en supervivencia libre de progresión y en la tasa de respuesta objetiva en el grupo combinación. Enfermedad localmente avanzada: PACIFIC: Actualización del estudio donde a 5 años de seguimiento, se puede ver que los resultados de durvalumab en supervivencia global y supervivencia libre de progresión demuestran un beneficio sostenido y clínicamente significativo a través del tiempo en los pacientes con CPCNP irresecable, tratados previamente con quimio-radiación concomitante. AFT-16: Estudio fase ll donde se combinó inmunoterapia neoadyuvante con atezolizumab cada 21 días por 12 semanas; si los pacientes presentaban progresión, recibían quimiorradioterapia. Enfermedad metastásica: CodeBreak 100: Resultados del estudio fase II, en donde se analizó la supervivencia global del estudio con sotorasib en pacientes con CPCNP, KRAS G12G, previamente tratados. AENEAS: Estudio fase lll, en pacientes con CPCNP localmente avanzado o metastásico sin tratamiento previo con deleción del exón 19 de EGFR o mutaciones L858R, donde se logró mejorar la supervivencia libre de progresión en el grupo con gefitinib. CheckMate-227: Estudio que se muestra prometedor con nivolumab + ipilimumab como tratamiento de primera línea en CPCNP avanzado. La combinación de nivolumab + ipilimumab demuestra beneficios a largo plazo, independientemente de la expresión o histología de PD-L1. CheckMate 9LA: Actualización a 2 años del estudio fase III, en donde se muestra una mejor supervivencia global en pacientes con CPCNP avanzado en combinación con nivolumab + ipilimumab. Resultados del análisis de eventos adversos relacionados con el sistema inmunológico, así como la eficacia de los estudios fase III: IMpower130, IMpower132 e IMpower150 con atezolizumab. Presentación de un análisis combinado de los estudios que evalúan quimioterapia + inmunoterapia vs. inmunoterapia sola como monoterapia en pacientes con PD-L1 entre 1 y 49%.

Go online to PeerView.com/KFC860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Advances in the management of patients with EGFR-mutated non-small cell lung cancer (NSCLC) have set a precedent for precision medicine. Genomic testing for EGFR mutations and use of EGFR-targeted therapies in appropriate patients have had an established role in the metastatic setting for many years, and they have recently expanded to early-stage disease. Based on impressive data, the FDA granted approval for the first EGFR tyrosine kinase inhibitor as adjuvant therapy following tumor resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. This approval has effectively changed the standard of care in the early-stage setting, with implications for the practice of the entire multidisciplinary team. This PeerView Live educational activity based on a recent web broadcast provides expert insights on the latest data and useful guidance for navigating the controversies, complexities of decision-making, and practicalities of multidisciplinary collaboration related to EGFR testing and EGFR-targeted therapy in early-stage NSCLC. Upon completion of this activity, participants should be better able to: Discuss the molecular heterogeneity of NSCLC and the oncogenic drivers such as EGFR mutations that help to inform treatment decisions regarding targeted therapies, Evaluate the latest safety and efficacy data on EGFR-targeted therapies in patients with early-stage EGFR-mutated NSCLC, Describe the evolving evidence and best practices for EGFR testing in lung cancer, including in early-stage NSCLC, Collaborate with the multidisciplinary team to integrate EGFR-targeted therapy into treatment plans for eligible patients with EGFR-mutated NSCLC, including in the adjuvant setting, according to recent evidence, precision oncology principles, and patient needs and preferences.

Go online to PeerView.com/KFC860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Advances in the management of patients with EGFR-mutated non-small cell lung cancer (NSCLC) have set a precedent for precision medicine. Genomic testing for EGFR mutations and use of EGFR-targeted therapies in appropriate patients have had an established role in the metastatic setting for many years, and they have recently expanded to early-stage disease. Based on impressive data, the FDA granted approval for the first EGFR tyrosine kinase inhibitor as adjuvant therapy following tumor resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. This approval has effectively changed the standard of care in the early-stage setting, with implications for the practice of the entire multidisciplinary team. This PeerView Live educational activity based on a recent web broadcast provides expert insights on the latest data and useful guidance for navigating the controversies, complexities of decision-making, and practicalities of multidisciplinary collaboration related to EGFR testing and EGFR-targeted therapy in early-stage NSCLC. Upon completion of this activity, participants should be better able to: Discuss the molecular heterogeneity of NSCLC and the oncogenic drivers such as EGFR mutations that help to inform treatment decisions regarding targeted therapies, Evaluate the latest safety and efficacy data on EGFR-targeted therapies in patients with early-stage EGFR-mutated NSCLC, Describe the evolving evidence and best practices for EGFR testing in lung cancer, including in early-stage NSCLC, Collaborate with the multidisciplinary team to integrate EGFR-targeted therapy into treatment plans for eligible patients with EGFR-mutated NSCLC, including in the adjuvant setting, according to recent evidence, precision oncology principles, and patient needs and preferences.

Go online to PeerView.com/KFC860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Advances in the management of patients with EGFR-mutated non-small cell lung cancer (NSCLC) have set a precedent for precision medicine. Genomic testing for EGFR mutations and use of EGFR-targeted therapies in appropriate patients have had an established role in the metastatic setting for many years, and they have recently expanded to early-stage disease. Based on impressive data, the FDA granted approval for the first EGFR tyrosine kinase inhibitor as adjuvant therapy following tumor resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. This approval has effectively changed the standard of care in the early-stage setting, with implications for the practice of the entire multidisciplinary team. This PeerView Live educational activity based on a recent web broadcast provides expert insights on the latest data and useful guidance for navigating the controversies, complexities of decision-making, and practicalities of multidisciplinary collaboration related to EGFR testing and EGFR-targeted therapy in early-stage NSCLC. Upon completion of this activity, participants should be better able to: Discuss the molecular heterogeneity of NSCLC and the oncogenic drivers such as EGFR mutations that help to inform treatment decisions regarding targeted therapies, Evaluate the latest safety and efficacy data on EGFR-targeted therapies in patients with early-stage EGFR-mutated NSCLC, Describe the evolving evidence and best practices for EGFR testing in lung cancer, including in early-stage NSCLC, Collaborate with the multidisciplinary team to integrate EGFR-targeted therapy into treatment plans for eligible patients with EGFR-mutated NSCLC, including in the adjuvant setting, according to recent evidence, precision oncology principles, and patient needs and preferences.

Go online to PeerView.com/KFC860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Advances in the management of patients with EGFR-mutated non-small cell lung cancer (NSCLC) have set a precedent for precision medicine. Genomic testing for EGFR mutations and use of EGFR-targeted therapies in appropriate patients have had an established role in the metastatic setting for many years, and they have recently expanded to early-stage disease. Based on impressive data, the FDA granted approval for the first EGFR tyrosine kinase inhibitor as adjuvant therapy following tumor resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. This approval has effectively changed the standard of care in the early-stage setting, with implications for the practice of the entire multidisciplinary team. This PeerView Live educational activity based on a recent web broadcast provides expert insights on the latest data and useful guidance for navigating the controversies, complexities of decision-making, and practicalities of multidisciplinary collaboration related to EGFR testing and EGFR-targeted therapy in early-stage NSCLC. Upon completion of this activity, participants should be better able to: Discuss the molecular heterogeneity of NSCLC and the oncogenic drivers such as EGFR mutations that help to inform treatment decisions regarding targeted therapies, Evaluate the latest safety and efficacy data on EGFR-targeted therapies in patients with early-stage EGFR-mutated NSCLC, Describe the evolving evidence and best practices for EGFR testing in lung cancer, including in early-stage NSCLC, Collaborate with the multidisciplinary team to integrate EGFR-targeted therapy into treatment plans for eligible patients with EGFR-mutated NSCLC, including in the adjuvant setting, according to recent evidence, precision oncology principles, and patient needs and preferences.

Go online to PeerView.com/KFC860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Advances in the management of patients with EGFR-mutated non-small cell lung cancer (NSCLC) have set a precedent for precision medicine. Genomic testing for EGFR mutations and use of EGFR-targeted therapies in appropriate patients have had an established role in the metastatic setting for many years, and they have recently expanded to early-stage disease. Based on impressive data, the FDA granted approval for the first EGFR tyrosine kinase inhibitor as adjuvant therapy following tumor resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. This approval has effectively changed the standard of care in the early-stage setting, with implications for the practice of the entire multidisciplinary team. This PeerView Live educational activity based on a recent web broadcast provides expert insights on the latest data and useful guidance for navigating the controversies, complexities of decision-making, and practicalities of multidisciplinary collaboration related to EGFR testing and EGFR-targeted therapy in early-stage NSCLC. Upon completion of this activity, participants should be better able to: Discuss the molecular heterogeneity of NSCLC and the oncogenic drivers such as EGFR mutations that help to inform treatment decisions regarding targeted therapies, Evaluate the latest safety and efficacy data on EGFR-targeted therapies in patients with early-stage EGFR-mutated NSCLC, Describe the evolving evidence and best practices for EGFR testing in lung cancer, including in early-stage NSCLC, Collaborate with the multidisciplinary team to integrate EGFR-targeted therapy into treatment plans for eligible patients with EGFR-mutated NSCLC, including in the adjuvant setting, according to recent evidence, precision oncology principles, and patient needs and preferences.

Go online to PeerView.com/KFC860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Advances in the management of patients with EGFR-mutated non-small cell lung cancer (NSCLC) have set a precedent for precision medicine. Genomic testing for EGFR mutations and use of EGFR-targeted therapies in appropriate patients have had an established role in the metastatic setting for many years, and they have recently expanded to early-stage disease. Based on impressive data, the FDA granted approval for the first EGFR tyrosine kinase inhibitor as adjuvant therapy following tumor resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. This approval has effectively changed the standard of care in the early-stage setting, with implications for the practice of the entire multidisciplinary team. This PeerView Live educational activity based on a recent web broadcast provides expert insights on the latest data and useful guidance for navigating the controversies, complexities of decision-making, and practicalities of multidisciplinary collaboration related to EGFR testing and EGFR-targeted therapy in early-stage NSCLC. Upon completion of this activity, participants should be better able to: Discuss the molecular heterogeneity of NSCLC and the oncogenic drivers such as EGFR mutations that help to inform treatment decisions regarding targeted therapies, Evaluate the latest safety and efficacy data on EGFR-targeted therapies in patients with early-stage EGFR-mutated NSCLC, Describe the evolving evidence and best practices for EGFR testing in lung cancer, including in early-stage NSCLC, Collaborate with the multidisciplinary team to integrate EGFR-targeted therapy into treatment plans for eligible patients with EGFR-mutated NSCLC, including in the adjuvant setting, according to recent evidence, precision oncology principles, and patient needs and preferences.

Go online to PeerView.com/KFC860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Advances in the management of patients with EGFR-mutated non-small cell lung cancer (NSCLC) have set a precedent for precision medicine. Genomic testing for EGFR mutations and use of EGFR-targeted therapies in appropriate patients have had an established role in the metastatic setting for many years, and they have recently expanded to early-stage disease. Based on impressive data, the FDA granted approval for the first EGFR tyrosine kinase inhibitor as adjuvant therapy following tumor resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. This approval has effectively changed the standard of care in the early-stage setting, with implications for the practice of the entire multidisciplinary team. This PeerView Live educational activity based on a recent web broadcast provides expert insights on the latest data and useful guidance for navigating the controversies, complexities of decision-making, and practicalities of multidisciplinary collaboration related to EGFR testing and EGFR-targeted therapy in early-stage NSCLC. Upon completion of this activity, participants should be better able to: Discuss the molecular heterogeneity of NSCLC and the oncogenic drivers such as EGFR mutations that help to inform treatment decisions regarding targeted therapies, Evaluate the latest safety and efficacy data on EGFR-targeted therapies in patients with early-stage EGFR-mutated NSCLC, Describe the evolving evidence and best practices for EGFR testing in lung cancer, including in early-stage NSCLC, Collaborate with the multidisciplinary team to integrate EGFR-targeted therapy into treatment plans for eligible patients with EGFR-mutated NSCLC, including in the adjuvant setting, according to recent evidence, precision oncology principles, and patient needs and preferences.

Go online to PeerView.com/KFC860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Advances in the management of patients with EGFR-mutated non-small cell lung cancer (NSCLC) have set a precedent for precision medicine. Genomic testing for EGFR mutations and use of EGFR-targeted therapies in appropriate patients have had an established role in the metastatic setting for many years, and they have recently expanded to early-stage disease. Based on impressive data, the FDA granted approval for the first EGFR tyrosine kinase inhibitor as adjuvant therapy following tumor resection in patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. This approval has effectively changed the standard of care in the early-stage setting, with implications for the practice of the entire multidisciplinary team. This PeerView Live educational activity based on a recent web broadcast provides expert insights on the latest data and useful guidance for navigating the controversies, complexities of decision-making, and practicalities of multidisciplinary collaboration related to EGFR testing and EGFR-targeted therapy in early-stage NSCLC. Upon completion of this activity, participants should be better able to: Discuss the molecular heterogeneity of NSCLC and the oncogenic drivers such as EGFR mutations that help to inform treatment decisions regarding targeted therapies, Evaluate the latest safety and efficacy data on EGFR-targeted therapies in patients with early-stage EGFR-mutated NSCLC, Describe the evolving evidence and best practices for EGFR testing in lung cancer, including in early-stage NSCLC, Collaborate with the multidisciplinary team to integrate EGFR-targeted therapy into treatment plans for eligible patients with EGFR-mutated NSCLC, including in the adjuvant setting, according to recent evidence, precision oncology principles, and patient needs and preferences.

Featuring perspectives from Drs Joel W Neal and Paul K Paik on the following topics: Introduction (0:00) Case: A 67-year-old man, never smoker with symptomatic metastatic adenosquamous carcinoma of the lung (1:33) Targeting ROS1 rearrangements in non-small cell lung cancer (NSCLC) (9:07) EGFR exon 19 deletion and exon 21 (L858R) point mutation in NSCLC (11:17) Recent data with agents targeting EGFR exon 20 insertions in NSCLC (28:22) Efficacy and safety of agents targeting HER2 amplification/mutation (31:56) ALK rearrangements as a therapeutic target in NSCLC (38:07) Targeting NTRK fusions in NSCLC (41:46) Available data with RET inhibitors in NSCLC (43:50) MET Exon 14 skipping mutations in NSCLC (46:36) Emerging data with agents targeting KRAS G12C mutation in NSCLC (51:47) CME information and select publications

In this episode, we review drugs recently approved by the Food and Drug Administration in the hematology/oncology space. David M. Mintzer, MD, of Pennsylvania Hospital, joins host David H. Henry, MD, to highlight some first-time approvals and new indications for older drugs. Approvals in 2020 Pembrolizumab (Keytruda) was approved for a range of new indications last year, including: First-line treatment of patients with unresectable or metastatic microsatellite instability–high or mismatch repair deficient colorectal cancer. https://bit.ly/2OKw8uF. Treatment of adult and pediatric patients who have tumor mutational burden–high (≥10 mutations/megabase) solid tumors that progressed after prior treatment and who have no satisfactory alternative treatment options. https://bit.ly/2NCddkX. For use in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer whose tumors express PD-L1 (combined positive score ≥10) as determined by an FDA-approved test. https://bit.ly/2ZobcMc. To treat patients with recurrent or metastatic cutaneous squamous cell carcinoma that is not curable by surgery or radiation. https://bit.ly/3ashYGV. Avelumab (Bavencio) was approved for maintenance therapy in patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy. https://bit.ly/3ar8XOs. Nivolumab (Opdivo) was approved for: Patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma after prior fluoropyrimidine- and platinum-based chemotherapy. https://bit.ly/3ar4bjX. Use in combination with ipilimumab as first-line treatment in adults with unresectable malignant pleural mesothelioma. https://bit.ly/2NbQ60V. Atezolizumab (Tecentriq) was approved in combination with cobimetinib and vemurafenib for patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. https://bit.ly/2NzkodG. Osimertinib (Tagrisso) was approved for adjuvant therapy after tumor resection in patients with non–small cell lung cancer whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. https://bit.ly/2NC0aQs. Selinexor (Xpovio) was approved for: Use in combination with bortezomib and dexamethasone for the treatment of adults with multiple myeloma who have received at least one prior therapy. https://bit.ly/3s1u1kp. Adults with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified, including disease arising from follicular lymphoma, after at least two lines of systemic therapy. https://bit.ly/2M172GW. The FDA also approved a new fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf (Phesgo) for subcutaneous injection for:  Use in combination with chemotherapy as neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer. Use in combination with chemotherapy as adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence. Use in combination with docetaxel to treat patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. https://bit.ly/2LXA4XX. Relugolix (Orgovyx) was the first oral gonadotropin-releasing hormone receptor antagonist approved by the FDA for adults with advanced prostate cancer. https://bit.ly/3qyJisQ. Approvals in 2021 Cemiplimab-rwlc (Libtayo) was approved for patients with locally advanced or metastatic basal cell carcinoma previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate. https://bit.ly/3ppkW31. Daratumumab plus hyaluronidase (Darzalex Faspro) was approved in combination with bortezomib, cyclophosphamide, and dexamethasone for newly diagnosed light chain amyloidosis. https://bit.ly/3bbaF5I. Approval in 2019 In late 2019, the FDA approved fam-trastuzumab deruxtecan-nxki (Enhertu) for patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. https://bit.ly/3qw9tA4. Show notes written by Sheila DeYoung, DO, a resident at Pennsylvania Hospital, Philadelphia. Disclosures Dr. Mintzer and Dr. Henry have no relevant disclosures. * * * For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd

With the advent of next generation sequencing, we've gained the ability to test for nearly any and all genomic alterations – many or most of which are benign or of uncertain significance. And, believe it or not, we encounter many benign or uncertain alterations in tumor related genes. Targeted therapies have historically been developed with a relatively small number of alterations in mind. For example, KRAS testing focused originally only on codon 12 and 13 mutations. While, 90% of deleterious EGFR alterations in lung #cancer are either chromosome 19 deletion or the L858R mutation. Are we in danger of watering down the size of the effect in clinical trials for targeted therapies by trying to incorporate too many genomic alterations in their #design?

Biomarker Assessment and Targeted Treatment of Nonsquamous Non-Small Cell Lung Cancer — A roundtable discussion with clinical investigators Drs Justin F Gainor, Matthew Gubens, Geoffrey R Oxnard and Heather Wakelee and general medical oncologists Drs Isaac Levy and Estelamari Rodriguez regarding biomarker analysis and related treatment decision-making for patients with non-small cell lung cancer. Biomarker testing and therapeutic decision-making for patients with non-small cell lung cancer (NSCLC) (00:00) Case: A woman in her late 80s, a never smoker, is diagnosed with metastatic adenocarcinoma of the lung with an EGFR exon 21 L858R mutation (01:56) Therapeutic approach for patients with NSCLC and EGFR tumor mutations (04:14) Results of the Phase III FLAURA trial evaluating osimertinib versus gefitinib or erlotinib for untreated advanced NSCLC with EGFR tumor mutations (06:08) Pneumonitis and cardiotoxicity associated with osimertinib in patients with NSCLC (09:56) Second-line therapy for patients after disease progression on osimertinib (13:25) Efficacy and tolerability of immune checkpoint inhibitors in patients with NSCLC harboring an actionable genomic alteration (17:08) Resistance mutations in patients who experience disease progression on osimertinib (18:58) Genomic profiling for patients with metastatic nonsquamous NSCLC; optimal testing platforms (24:38) Evaluation of biomarkers in patients with squamous cell carcinoma of the lung (28:54) Targeting KRAS G12C and MET exon 14 splice mutations  (31:39) Case: A woman in her mid-50s who presents with cough, dyspnea and respiratory distress is diagnosed with metastatic adenocarcinoma of the lung with an EGFR exon 21 L858R mutation (36:15) Considerations for switching to an EGFR tyrosine kinase inhibitor (TKI) in a symptomatic patient initially started on chemotherapy prior to the identification of an EGFR tumor mutation (38:18) Role of liquid biopsy in monitoring patients who are receiving EGFR TKI therapy (40:56) Activity of immune checkpoint inhibitors in patients with NSCLC and targetable genomic alterations (44:35) Results of the IMpower150 and IMpower130 trials of atezolizumab with bevacizumab/chemotherapy and atezolizumab with chemotherapy, respectively, as first-line treatment for metastatic nonsquamous NSCLC (47:32) Immune checkpoint inhibitors for patients with advanced lung cancer with oncogenic driver alterations: Results from the IMMUNOTARGET registry (50:37) Toxicities associated with the use of targeted therapy after immunotherapy in patients with NSCLC; risk of pneumonitis with durvalumab and osimertinib (53:33) Increased hepatotoxicity associated with sequential immune checkpoint inhibitor and crizotinib therapy for patients with NSCLC (56:20) Therapeutic approach for patients with locally advanced NSCLC with EGFR tumor mutations who experience disease relapse after treatment with durvalumab (59:10) Cardiac toxicity associated with immune checkpoint inhibitors (1:03:56) Monitoring for and management of the cardiac side effects of immune checkpoint inhibitors (1:06:52) Case: A man in his late 70s with adenocarcinoma of the lung and brain metastases is found through next-generation sequencing to have an EGFR exon 21 L858R mutation, HER2 amplification and high PD-L1 expression (1:09:58) Use of liquid biopsy to detect genomic alterations in patients with NSCLC (1:11:22) FGFR alterations in patients with NSCLC (1:14:42) Targeting HER2 alterations in patients with lung cancer (1:16:27) Efficacy of EGFR TKIs in patients with lung cancer and CNS metastases; sequencing stereotactic radiosurgery and EGFR TKIs (1:18:22) Diagnosis and management of radiation necrosis in patients with lung cancer (1:22:26) Preservation of neurocognitive function during whole-brain radiation therapy with hippocampal sparing for patients with NSCLC and brain metastases (1:25:33) Case: A woman in her early 80s with adenocarcinoma of the lung with an EGFR exon 21 L858R mutation and metastases to the brain receives osimertinib as first-line therapy (1:27:11) Activity of EGFR TKIs in patients with brain metastases; CNS penetration and dosing of osimertinib (1:30:59) Results of the BLOOM study evaluating osimertinib for patients with leptomeningeal metastases from NSCLC with EGFR tumor mutations (1:34:34) Targeting EGFR exon 20 insertions with TAK-788 and poziotinib (1:36:12) Results of the Phase III ALEX study evaluating alectinib and the Phase III ALTA-1L study investigating brigatinib for patients with advanced NSCLC and ALK rearrangements (1:39:36) Sequencing ALK inhibitors for patients with NSCLC with ALK rearrangements (1:42:08) Tolerability of brigatinib, alectinib, ceritinib and lorlatinib in patients with NSCLC with ALK rearrangements (1:45:41) Emerging data with targeted therapies for patients with NSCLC in the (neo)adjuvant setting (1:50:16) Ongoing (neo)adjuvant trials of targeted therapies for patients with locally advanced NSCLC (1:52:38) Perspective on emerging data from studies evaluating adjuvant targeted therapy for advanced NSCLC (1:55:56) Risks associated with neoadjuvant therapy for patients with advanced NSCLC (1:59:02) Case: A woman in her late 50s with metastatic NSCLC with a RET rearrangement receives carboplatin/pemetrexed/bevacizumab followed by selpercatinib upon disease progression (2:01:04) Activity of the selective RET inhibitors selpercatinib and pralsetinib; detection of RET alterations in patients with NSCLC (2:05:48) Duration of response, CNS penetration and tolerability profile of RET inhibitors (2:08:56) Efficacy of pemetrexed-based chemotherapy regimens for patients with NSCLC with RET fusions (2:12:33) Case: A woman in her mid-50s with metastatic NSCLC with a BRAF V600E tumor mutation attains a good response to dabrafenib/trametinib after experiencing disease progression on multiple lines of therapy (2:15:05) Activity and tolerability of BRAF and MEK inhibitors in patients with NSCLC with BRAF tumor mutations (2:17:26) Duration of therapy with BRAF and MEK inhibitors (2:19:47) Biology, detection and management of NSCLC with MET exon 14 mutations (2:22:35) Significance of HER2 mutations in patients with lung cancer (2:26:43) Targeting NTRK gene fusions with larotrectinib and entrectinib (2:29:44) Therapeutic options for patients with NSCLC and ROS1 translocations (2:35:52) CME information and select publications

This podcast describes the results of the BLOOM study, evaluating the efficacy of osimertinib in EGFR-mutated lung cancer with leptomeningeal disease after failure of prior EGFR TKI therapy. TRANSCRIPT This JCO Podcast provides observations and commentary on the JCO article “Osimertinib In Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study” by Yang et al. My name is Jürgen Wolf and I am the medical director of the Center for Integrated Oncology at the University Hospital of Cologne in Germany. I am a medical oncologist with expertise in personalized lung cancer care.   About 10% of patients with advanced EGFR-mutated lung cancer suffer from leptomeningeal disease. While this disease manifestation in non-small-cell lung cancer is generally associated with a particularly poor prognosis, with survival times of only a few months, the question arises whether treatment with specific tyrosine kinase inhibitors might enable a better disease control. Most studies evaluating the efficacy of 1st and 2nd generation EGFR-TKIs in leptomeningeal disease were retrospective and difficult to interpret, given the heterogeneity of the disease as well as of the preceding treatment procedures. Small prospective studies with patient numbers below 20 tested standard dose erlotinib or afatinib as well as high-dose pulsatile EGFR TKI treatment and reported disappointing results with survival times of around 4 months only.   The 3rd generation EGFR TKI osimertinib initially was approved for T790M positive failure of 1st and 2nd generation EGFR TKIs and is now commonly regarded as 1st line standard treatment for EGFR-mutated lung cancer based on a superior progression-free survival, overall survival and toxicity profile. In studies with primates and healthy volunteers, osimertinib has been shown to exert a higher blood-brain barrier permeability and a higher brain exposure compared with other TKIs. In the AURA clinical development program for osimertinib, 22 patients with T790M-positive relapse after EGFR TKI treatment and leptomeningeal disease were retrospectively identified, and an impressive median overall survival of 18.8 months was reported. A small prospective Japanese trial evaluated osimertinib in 13 patients with T790M-positive leptomeningeal disease which, however, could be confirmed only in 5 patients. Responses were seen in some patients, and the median progression free survival for all patients was reported with 7.2 months.   The BLOOM study part B, which is discussed in this podcast, is a multicenter phase I study evaluating osimertinib in EGFR-mutated lung cancer patients with leptomeningeal metastases and failure of previous EGFR TKI treatment. Study objectives were the assessment of clinical parameters like response, overall survival neurological status, and safety but also pharmacokinetics in blood and cerebrospinal fluid. Main inclusion criteria included confirmed diagnosis of EGFR Exon 19 deletion or L858R mutation and confirmation of leptomeningeal disease by positive cytology of cerebrospinal fluid and at least one leptomeningeal site assessable by MRI. There were two sequential cohorts, one unselected for the T790M mutation and with stable non-CNS disease at enrollment, and one for T790M positive patients without the requirement for stable non-CNS disease. Osimertinib dose was 160 mg once daily, which is twice the approved dose. Besides investigator-based response assessment, according to RECIST, leptomeningeal disease was also assessed by a neuroradiological blinded central review according to the RANO-LM working group criteria, which integrates clinical examination, cerebrospinal fluid cytology and neuraxis MRI.   41 patients from South Korea and Taiwan were included, 20 in the unselected and 21 in the T790M-positive cohort. About 70% of the patients had co-existing brain mets and about 50% prior radiotherapy. For 4 patients, no response data from the independent review were available.   The confirmed overall response rate for leptomeningeal disease was impressive at 62% as assessed by blinded independent review and nearly identical between both cohorts.  By comparison, the overall response rate was only 27% by investigator assessment, which, in turn, revealed a higher stable disease rate. Prior brain radiotherapy had no influence on efficacy. Median duration of response was comparable between blinded independent review and investigator, with 15.2 and 18.9 months, respectively. In about one third of the evaluable patients confirmed CSF clearance could be observed. PK analysis indicated that plasma concentration of osimertinib and its active metabolites reached steady state by day 15; the ratio for osimertinib exposure in cerebrospinal fluid vs. plasma was around 16%.   Surprisingly, only half of the patients had an abnormal neurological baseline assessment, most of them with mild symptoms. Symptom stabilization occurred in 54% during treatment; only 5% showed regression of neurological functions.   Overall, median progression-free survival, as assessed by the investigators, was 8.6 months and median overall survival 11 months. Progression-free survival and overall survival differed markedly between both cohorts. For instance, overall survival was 16.6 months in the unselected and 8.1 months in the selected group. Possibly, the requirement for stable non-CNS disease in the unselected group was partly responsible for the better survival outcome in this subset . However, this has to be interpreted cautiously in view of small patient numbers and large confidence intervals.   Osimertinib 160mg was well tolerated in the majority of patients with the known osimertinib side-effect profile. However, 24% of the patients suffered from adverse events grade 3 or more—possibly related to osimertinib, according to the investigators’ assessment. Dose reduction had to be performed in 12% and discontinuation of treatment in 22% of the patients due to adverse events. 17% of the patients had fatal events that did not appear to be causally related to osimertinib.   What can we learn from this study? This is the largest prospective study so far in this setting and osimertinib clearly shows clinical efficacy. The study methodology was sound, with response assessment by blinded independent review and based on RECIST criteria as well as on the RANO criteria established in particular for leptomeningeal disease. The overall response rate of leptomeningeal disease of around 60% and the duration of response of around 15 months is clinically relevant in particular, as it is correlated with improvement or at least neurological stabilization in most patients. Although the toxicity of the treatment is substantially higher than reported in osimertinib trials so far, it is manageable, and the risk/benefit ratio appears to be favorable.   What are the limitations of the study? Patient numbers are small, and the patients are heterogeneous with respect to several important factors such as pretreatment whole-brain radiotherapy, occurrence of simultaneous CNS metastases and neurological symptoms. Thus, absolute values for efficacy have to be interpreted cautiously, and comparison with already published trials remains difficult. Also, unfortunately in view of the toxicity, the question remains open whether the 160mg dose, which is not approved, is actually necessary. Finally, since osimertinib increasingly becomes the first-line treatment standard in EGFR-mutated lung cancer, the number of patients with failure of 1st- or 2nd-generation EGFR TKI treatment will decrease.   Despite these limitations, the trial provides the most convincing data so far in this special patient population and, in my opinion, defines  an important new option to consider for patients with EGFR-mutated lung cancer and leptomeningeal disease after failure of previous EGFR TKI treatment.   This concludes this JCO Podcast. Thank you for listening.

There are sub-types within the sub-type of EGFR mutation positive lung cancer. In this presentation, Dr. Jack West discuss the different activating mutations within EGFR positive tumors and how they impact treatment.

There are sub-types within the sub-type of EGFR mutation positive lung cancer. In this presentation, Dr. Jack West discuss the different activating mutations within EGFR positive tumors and how they impact treatment.

There are sub-types within the sub-type of EGFR mutation positive lung cancer. In this presentation, Dr. Jack West discuss the different activating mutations within EGFR positive tumors and how they impact treatment.

Drs. Leora Horn, Ben Solomon, & Jack West discuss the open question of whether there are clinically significant differences among leading EGFR tyrosine kinases based on the specific EGFR mutation to be treated.

Drs. Leora Horn, Ben Solomon, & Jack West discuss the open question of whether there are clinically significant differences among leading EGFR tyrosine kinases based on the specific EGFR mutation to be treated.

Drs. Leora Horn, Ben Solomon, & Jack West discuss the open question of whether there are clinically significant differences among leading EGFR tyrosine kinases based on the specific EGFR mutation to be treated.

Dr. Greg Reily from MSKCC provides an introduction to the epidermal growth factor receptor (EGFR), what an EGFR mutation means, and which patients are more likely to have them.

Dr. Greg Reily from MSKCC provides an introduction to the epidermal growth factor receptor (EGFR), what an EGFR mutation means, and which patients are more likely to have them.

Dr. Greg Reily from MSKCC provides an introduction to the epidermal growth factor receptor (EGFR), what an EGFR mutation means, and which patients are more likely to have them.

Dr. Jack West, medical oncologist, reviews evidence in favor of adding Avastin (bevacizumab) to the EGFR inhibitor Tarceva (erlotinib) for patients with lung cancer that harbors an activating EGFR mutation.

Dr. Jack West, medical oncologist, reviews evidence in favor of adding Avastin (bevacizumab) to the EGFR inhibitor Tarceva (erlotinib) for patients with lung cancer that harbors an activating EGFR mutation.

Dr. Jack West, medical oncologist, reviews evidence in favor of adding Avastin (bevacizumab) to the EGFR inhibitor Tarceva (erlotinib) for patients with lung cancer that harbors an activating EGFR mutation.