Podcast appearances and mentions of heather wakelee

Featuring perspectives from Dr Heather Wakelee, including the following topics: Introduction (0:00) Cases: A man in his late 50s with metastatic carcinoma of the lung, no actionable genomic alteration (AGA), PD-L1-negative, and a man in his early 60s with metastatic squamous cell carcinoma of the lung, PD-L1-negative — Brian P Mulherin, MD and Taral Patel, MD (8:08) Case: A man in his late 60s presenting with metastatic adenocarcinoma of the lung, multiple bone metastases, no AGA; PD-L1 20%; enrolled on ECOG-EA5163 — Priya Rudolph, MD, PhD (21:45) Current and Emerging Immunotherapeutic Strategies for Metastatic Non-Small Cell Lung Cancer (mNSCLC) (30:55) Case: An African American man in his early 60s with 6.2-cm squamous cell carcinoma of right upper lung receives neoadjuvant treatment as per CheckMate 816 — Dr Rudolph (39:16) Case: A man in his late 60s with pT2aN0 invasive adenocarcinoma of the right lower lung, no AGA; PD-L1 5% — Zanetta S Lamar, MD (44:57) Antibody-Drug Conjugates and Other Management Approaches for mNSCLC without AGAs (48:51) Case: A woman in her early 60s diagnosed in 2014 with metastatic adenocarcinoma of the lung treated on ECOG 5508 (carboplatin/paclitaxel/bevacizumab) receives nivolumab on disease progression — Dr Rudolph (56:35) CME information and select publications

Dr Heather Wakelee from Stanford University School of Medicine in California discusses the implications of recent datasets for the current and future use of nontargeted therapy for metastatic non-small cell lung cancer.

Dr Heather Wakelee from Stanford University School of Medicine in California discusses the implications of recent datasets for the current and future use of nontargeted therapy for metastatic non-small cell lung cancer, moderated by Dr Neil Love. Produced by Research To Practice. CME information and select publications here (https://www.researchtopractice.com/MTPWLE24).

Please visit answersincme.com/CFN860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, two experts in oncology discuss current and emerging treatments for unresectable stage I to III EGFR mutation–positive non–small-cell lung cancer. Upon completion of this activity, participants should be better able to: Review best practices for integrating biomarker testing into practice for stage I to III NSCLC; Describe the clinical profiles of current and emerging therapeutic approaches for the management of stage I to III NSCLC; and Outline multidisciplinary strategies to optimize the integration of a targeted approach into clinical practice for patients with stage I to III NSCLC.

Please visit answersincme.com/TAR860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, an expert in oncology discusses the integration of perioperative immunotherapy-based regimens for the treatment of resectable non–small-cell lung cancer (NSCLC). Upon completion of this activity, participants should be better able to: Recognize the rationale for the use of neoadjuvant followed by adjuvant immunotherapy-based regimens in patients with resectable NSCLC; Describe current evidence on the use of neoadjuvant plus adjuvant immunotherapy in patients with resectable NSCLC; and Outline practical strategies to integrate neoadjuvant plus adjuvant immunotherapy-based regimens into the treatment plan for appropriate patients with resectable NSCLC.

Featuring perspectives from Dr Tanios Bekaii-Saab, Dr Harold Burstein, Dr Asher Chanan-Khan, Dr Komal Jhaveri, Dr Brad S Kahl, Dr Alicia K Morgans, Dr Philip A Philip, Dr Gregory J Riely, Dr Matthew R Smith and Dr Heather Wakelee, including the following topics: Introduction (0:00) Non-Small Cell Lung Cancer Targeted Therapy — Dr Riely (4:09) Non-Small Cell Lung Cancer: Immunotherapeutic and Other Novel Strategies — Dr Wakelee (32:23) CME information and select publications

Featuring perspectives from Dr Tanios Bekaii-Saab, Dr Harold Burstein, Dr Asher Chanan-Khan, Dr Komal Jhaveri, Dr Brad S Kahl, Dr Alicia K Morgans, Dr Philip A Philip, Dr Gregory J Riely, Dr Matthew R Smith and Dr Heather Wakelee, including the following topics: Introduction (0:00) Chronic Lymphocytic Leukemia (CLL): Considerations for Front-Line Treatment — Dr Kahl (1:48) Treatment of Relapsed/Refractory CLL; Novel and Investigational Strategies — Dr Chanan-Khan (35:38) Clinical Questions and Cases (49:58) CME information and select publications

Featuring perspectives from Dr Tanios Bekaii-Saab, Dr Harold Burstein, Dr Asher Chanan-Khan, Dr Komal Jhaveri, Dr Brad S Kahl, Dr Alicia K Morgans, Dr Philip A Philip, Dr Gregory J Riely, Dr Matthew R Smith and Dr Heather Wakelee, including the following topics: Introduction (0:00) Gastroesophageal Cancers — Dr Philip (1:42) Colorectal Cancer — Dr Bekaii-Saab (32:56) CME information and select publications

Featuring perspectives from Dr Tanios Bekaii-Saab, Dr Harold Burstein, Dr Asher Chanan-Khan, Dr Komal Jhaveri, Dr Brad S Kahl, Dr Alicia K Morgans, Dr Philip A Philip, Dr Gregory J Riely, Dr Matthew R Smith and Dr Heather Wakelee, including the following topics: Introduction (0:00) Role of Hormonal Therapy in Prostate Cancer Management — Dr Smith (1:50) Clinical Questions and Cases (13:18) Evidence-Based Use of Other Therapeutic Approaches in Metastatic Castration-Resistant Prostate Cancer — Dr Morgans (26:08) Clinical Questions and Cases (38:01) CME information and select publications

Featuring perspectives from Dr Tanios Bekaii-Saab, Dr Harold Burstein, Dr Asher Chanan-Khan, Dr Komal Jhaveri, Dr Brad S Kahl, Dr Alicia K Morgans, Dr Philip A Philip, Dr Gregory J Riely, Dr Matthew R Smith and Dr Heather Wakelee, including the following topics: Introduction (0:00) ER-Positive Breast Cancer — Dr Burstein (3:57) Clinical Questions and Cases (16:47) Selection and Sequencing of Treatment for Relapsed ER-Positive Metastatic Breast Cancer — Dr Jhaveri (33:32) Clinical Questions and Cases (46:02) CME information and select publications

From lung cancer in women to gender equity in the healthcare workforce, IASLC is privileged to host HRH Princess Dina Mired of Jordan at the 2023 World Conference on Lung Cancer. In this special episode of Lung Cancer Considered, host Dr. Narjust Florez, IASLC President Dr. Heather Wakelee, and WCLC 2023 co-chair Dr. Fiona Hegi-Johnson discuss global advocacy through a gender equity lens, lessons learned from the field, and how HRH Dina Mired's experience as the mother of a cancer survivor has impacted her work and initiatives globally.

Non-small cell lung cancer was one of the big topics at the 2023 ASCO Annual Meeting where Heather Wakelee, MD, FASCO, Professor of Medicine and Chief of the Division of Oncology at Stanford University in California, was overheard reminding a junior cancer doctor that the only adjuvant therapy for lung cancer had been chemotherapy just a couple of decades previously. Now, a plethora of targeted therapies are available, and Wakelee reported a big improvement in outcome from one of them—pembrolizumab—used both before and after surgery in early Stage II and III disease (mostly Stage III). “These results indicate perioperative pembrolizumab given in combination with chemotherapy prior to surgery and for up to one year as a single agent after surgery led to significant improvement in event-free survival (defined by local progression precluding definitive surgery, recurrence, or death) with a strong trend towards improvement in overall survival. These results indicate peri-operative pembrolizumab significantly improves outcomes for patients with potentially resectable Stage II-III NSCLC,” said Wakelee. After her talk at ASCO, she discussed her group’s findings with OncTimesTalk correspondent, Peter Goodwin.

Drs. Vamsi Velcheti and Jack West discuss ADAURA, KEYNOTE-671, and KEYNOTE-789 trials in NSCLC and the first pivotal study of sunvozertinib for the treatment of NSCLC with EGFR exon 20 insertion mutations. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast. I'm a professor of medicine and director of thoracic medical oncology at the Perlmutter Cancer Center at NYU Langone Health. My guest today is Dr. Jack West, a thoracic oncologist and associate professor in medical oncology at City of Hope Comprehensive Cancer Center. Today, we'll be discussing practice-changing studies and other key advances in lung cancer that were featured at the 2023 ASCO Annual Meeting.   Our full disclosures are available in the transcript of this episode and disclosures of all guests on the ASCO Daily News podcast are available at asco.org/DNpod.   Jack, there was a lot of exciting new data that emerged from the ASCO Annual Meeting, and it's great to have you back on our podcast today to talk about all the key updates in lung cancer.   Dr. Jack West: Absolutely. Thanks so much. It's always a high-energy meeting, and there was a lot to talk about in the lung cancer sessions this year for sure.  Dr. Vamsi Velcheti: Let's begin with LBA3, the ADAURA trial. This was presented in the Plenary Session at ASCO; we've heard previously the DFS updates from previous meetings, and overall survival updates were presented at the ASCO 2023 Annual Meeting. So, Jack, what was the highlight of the presentation for you? And could you put things in context for us? We have known about the DFS data for a while now. What gets you so excited about this study?  Dr. Jack West: Well, we've actually been focused on this trial for literally 3 years, since Dr. Herbst presented it at another Plenary presentation back in the ASCO Meeting in 2020 when we saw tremendous differences in the DFS data. Again, this was a trial of patients with resected stage 1b to 3a EGFR mutation-positive non-small cell lung cancer. Nearly 700 patients were randomized to after-surgery, and for many, but not all, patients undergoing chemotherapy, it wasn't mandated. But after that, they were randomized to get adjuvant, placebo, or osimertinib for up to 3 years. And we saw huge differences in the disease-free survival from the first presentation, with a hazard ratio in the range of 0.2.   We have notably seen significant improvements in disease-free survival before with other EGFR TKIs for this population after surgery, but nothing in this range. And it's also notable that in the various other trials of other EGFR inhibitors in the postoperative setting, we've seen a DFS benefit, but that didn't translate to an improvement in overall survival. So, seeing a press release that this was associated with a significant and, in fact, highly significant by report, improvement in overall survival, as well as DFS, was really notable.   What's also, I think, particularly important as a focus of this is that in the later presentations of this work, with longer follow-up last year, we saw that the DFS curves showed a drop in the DFS starting after these patients had completed 3 years of treatment. So, really suggesting that at least some, if not many or most of these patients who had been on adjuvant osimertinib were subject to a higher risk of relapse once they completed that. So, again, making the endpoint of overall survival particularly important. It's always been to me the endpoint we should care about most in a curative setting. Although the DFS was the primary endpoint of the study and it was powered and built around specifically focusing on the DFS difference, so overall survival was reassuring, I think, when we actually saw it, but not what the trial was centered around.    And what we saw was a very dramatic improvement in overall survival with a hazard ratio of 0.49. That was essentially the same for the patients with stage 2 to 3a disease, as well as the broader population with stage 1b to 3a disease. When we look at the absolute numbers for overall survival at 5 years, there was an improvement from 73% to 85% with osimertinib, and in the population from 1b to 3a, an improvement from 78% to 88%. So, many things to comment on here. Really remarkable to see an 88% 5-year survival in the osimertinib arm that includes patients with stage 3a disease.    I would say that there's still some controversy, some questions about this, and it really centers around a few things. One is, like many global trials, this one enrolled patients from many places that did not have the same standard of care staging that we follow in the U.S. There wasn't any specification or mandate for PET scans, which would be very routine in the U.S. And brain MRIs were not mandated either. And so there were almost certainly some patients with more advanced disease that was not detected that would be a big advantage for the osimertinib arm, but really not characterized. And also, the crossover was made possible to osimertinib starting in April of 2020, but only 38.5% of the patients on the control arm actually received osimertinib at the time of relapse. And even though many of the other patients who had a relapse did get another EGFR inhibitor, I don't think there's much question that osimertinib is the preferred and optimal EGFR TKI.   And so there were a couple of important factors kind of going for this trial. One is the long, long, long duration of treatment at 3 years, though with a drop-off, I think some questions about whether even that is enough, and we might be tempted to treat beyond 3 years. And then how much did the inability of most of the patients on the control arm to get osimertinib later contribute? My personal view is that it is a troubling aspect of this trial. But also so many other trials that they're run globally in places where we arguably perpetuate these disparities by running these trials that, in part, magnify the differences between the two arms because some patients just will not have access to what is our best standard of care in the U.S., or many other parts of the world, but weren't necessarily available to many of the patients on the control arm where it was conducted. So, I think that's always a concern. It's definitely an issue of this trial, but I would not say it's unique to this one.  Dr. Vamsi Velcheti: Very good points, Jack, and I completely agree with you. I think those certainly are concerns. But on the other hand, this is a pragmatic trial and that's the real-world scenario in terms of access issues, in terms of osimertinib globally, correct, in the stage 4 setting, even though we all agree that osimertinib is the best option for patients with metastatic EGFR-mutated lung cancer, I think that's obviously a reflection of global access issues and global disparities and changes in standard of care in terms of workup as well. So, it's somewhat of a pragmatic trial in some ways and I completely agree with you, I think that may have potentially had some impact on the overall survival.  Dr. Jack West: Well, I would clarify that I don't think that this really highly significant difference in overall survival is undermined completely by this. There's no question in my mind that with the huge difference in disease-free survival that we'd already seen for 3 years, it has become our standard of care really for this population at least to offer it, if not to strongly recommend it. But I would say that most of us have been quite inclined to recommend it, perhaps with caveats. And I would say that this overall survival benefit mostly corroborates that, even if there are some concerns about how these trials are done, but it's still an impressive difference that would lead me to only cement my practice of pursuing it in this setting. I just would love to re-examine how we conduct these trials and potentially potentiate disparities that exist and don't want to have our trials be more positive by capitalizing on that.   Dr. Vamsi Velcheti: Let's move on to the next abstract, LBA100; this is the KEYNOTE-671 trial. This was featured during the meeting's Clinical Science Symposium. This is a study of pembrolizumab or placebo plus platinum doublet followed by surgical resection and pembrolizumab or placebo for early-stage non-small cell lung cancer. Jack, what was the key message from this trial, and do you consider this as practice-changing?  Dr. Jack West: This has been an area where we've seen really dramatic evolution in our practice patterns, specifically, at least for patients who don't have a tumor harboring an EGFR mutation or ALK rearrangement. I would say that there has been some momentum toward preoperative neoadjuvant therapy, specifically based on the CheckMate-816 trial that gave chemo with nivolumab versus placebo and showed a significant improvement in the pathologic complete response rate at surgery as well as event-free survival. The overall survival looks encouraging but is still early and hasn't met the threshold for statistical significance, and that's FDA-approved.   But we still question whether there's a value to doing anything in the postoperative setting. And the CheckMate-816 trial did not include that as part of the trial. It allowed postoperative management at the judgment of the treating physician but didn't really prescribe anything. We now have the results of several trials in the last few months that have added a component in the postoperative setting in addition to three or four cycles of preoperative chemoimmunotherapy. And the first one that gave us a glimpse was the AEGEAN trial presented by Dr. John Heymach at AACR in April of this year that looked at chemo and durvalumab versus chemo placebo and then followed by a year of durvalumab versus placebo after surgery. That showed results in terms of major pathologic response and event-free survival that are significantly better with immunotherapy. Not clearly superior to what we would see with CheckMate-816.   And then even more recently, we saw a monthly Plenary presentation from ASCO with the Neotorch trial presented by Dr. Shun Lu of China. This was a Chinese trial only that presented results just for patients with stage 3 disease thus far. This included patients with stage 2 or stage 3, but what we saw is stage 3 results and that looked at chemo with toripalimab for 3 cycles versus placebo and then a year of checkpoint inhibitor or placebo. This also shows a benefit with the addition of immunotherapy, but not clear if that's better than what we can already achieve with neoadjuvant alone with the Checkmate-816 approach.   And then what we have now is a presentation and simultaneous publication by Dr. Heather Wakelee of KEYNOTE-671. And this is really almost the exact same trial design as AEGEAN. It's 4 cycles of platinum doublet chemotherapy and it is for patients with stage 2 to 3a disease. And this gave 4 cycles of chemotherapy with placebo or pembrolizumab. And then after surgery, patients would go on in the investigation arm to a year of pembrolizumab or to the additional year with placebo. And this shows a significant improvement in event-free survival with a hazard ratio of 0.58. It's most prominent in patients with high PD-L1, where the hazard ratio is 0.42. But there's still a benefit in patients with PD-L1 less than 1%, where it's 0.77. And there was a trend toward better overall survival here, hazard ratio of 0.73. It does not reach statistical significance at this early point. It's still preliminary but certainly looks encouraging. And there are also significant improvements in major pathologic response, where less than 10%, about a threefold difference from 30.2% with immunotherapy compared to 11% with placebo. And a very impressive improvement in pCR rate, which is 18.1% with the chemo and pembro compared to 4% with chemotherapy alone. Not surprisingly, when we look at event-free survival, it's best in the patients who achieve a pathologic complete response, but pembrolizumab improved outcomes in event-free survival even for those who didn't achieve a pCR.   The real question I would say is does the addition of a year of checkpoint inhibitor therapy postoperatively add to what we already achieve with those first three cycles with chemo-neo or 4 cycles with maybe one of these other options? And these trials can't answer that question because they just include them as a package deal. There's no way to tease apart right now the component of what incremental benefits you get from that. And it certainly adds a year of time coming in for every 3-week infusions. Even if you space that out, it's still a year of coming in and getting infusions, potential cumulative immune-related toxicities, and a lot of cost versus potentially being done. And I think that really is the big question at this point of do you want to recommend something when we don't really have a precedent for much benefit beyond the first 4 cycles? Perhaps. Certainly, we give maintenance pemetrexed and other immunotherapies and there can be benefit there. So, I wouldn't say you necessarily cap that. But if there is resistant disease after the first 4 cycles you've already given 3 cycles, how much benefit is there? How likely is it that you're going to eradicate the last cancer cells with more?   That said, I think many patients, and oncologists myself perhaps included, are going to be inclined to err on the side of possibly over-treating, but at least trying to give everything that is part of a widely studied, FDA-approved approach once these options become available. I just think it's going to end up as a careful discussion with each patient about whether they'd prefer to just say they're done or do that extra year and really feel that even if it comes back, they've done everything that made sense to try.  Dr. Vamsi Velcheti: Very good points, Jack. So let's move on to another abstract, which is the LBA9000. This is the KEYNOTE-789 trial. In my opinion, this is the most important negative phase 3 trial in lung cancer in a while. This is a trial looking at pemetrexed platinum with or without pembrolizumab in patients who have EGFR mutation-positive metastatic non-small cell lung cancer. So, what are your key takeaways, Jack?  Dr. Jack West: Well, I would say essentially we've been waiting to figure out what is the best treatment approach for patients with acquired resistance after osimertinib. And most of the patients had received osimertinib for their EGFR mutation-positive non-small cell. This is essentially KEYNOTE-189 being run in the EGFR mutation-positive patients after they've exhausted at least the major benefit of EGFR TKI therapy.   What we saw was a hazard ratio for progression-free survival of 0.8. It didn't quite make it across the threshold for efficacy, a significant difference. And so it missed that efficacy boundary. And overall survival, the hazard ratio is 0.84, also missing the efficacy boundary. When you look at the actual curves, they show modest separation, nothing eye-popping, certainly compared to some of the other trials we're talking about. But I wouldn't say they show no benefit. And I think that's, to me, why there's really still a role for a nuanced thought process and maybe some discussion about how negative this is. This is not, in my mind, stone-cold negative with no patients benefiting from immunotherapy. This is a trial that really suggests that there's a subset of patients who are benefiting from immunotherapy.   And we've also seen going back to subset analysis of the IMpower150 trial and also the ORIENT-31 trial with sintilimab and a bevacizumab biosimilar, another anti-VEGF inhibitor. These trials both really indicated a benefit in this population after EGFR TKI therapy of immunotherapy combined with VEGF. I think there could still be a value in there. I don't want to be a Pollyanna or too open-minded, but I think that there was at least a suggestion that this could still be a fruitful avenue. I think that this is still something we should do additional studies on that could bear fruit. I wouldn't close the door and categorically say this is just never going to translate to any benefit for any of these patients.   Dr. Vamsi Velcheti: The key thing, though, is, like in EGFR mutant patients I think in the previous studies as well, the response rates with single-agent PD-1 have been very minimal. And I think one of the things that's actually very important to highlight is in the operative setting, the early-stage setting, unfortunately, some of the trials with immunotherapy have included patients with an EGFR mutation. And now we have a treatment option for those patients within the adjuvant setting, especially osimertinib. We just heard from the ADAURA trial, which has a clear significant overall survival benefit. So I think it's really important to test for EGFR mutation in all stages. And if somebody with the early stage has an EGFR mutation, adjuvant immunotherapy, or perioperative immunotherapy may not be the best option for those patients.  Dr. Jack West: Right. I agree with that, although it is interesting that the KEYNOTE-671 trial did have some small population of patients with an EGFR mutation, and in that subset analysis, they seem to benefit from the pembrolizumab. I would not say that we should divert from ADAURA, but I'm just not as sure that our previous statement and mindset that immunotherapy just categorically doesn't work for patients with driver mutations is that simple.   First of all, there is some heterogeneity about which driver mutation, and the ALK-positive patients seem to really get no benefit. But I think there's still some questions about immunotherapy for EGFR. Certainly, patients with KRAS or BRAF V600E seem to benefit like the broader range of patients. And I would also say maybe it's different whether you're giving immunotherapy combined with chemotherapy versus as monotherapy. So that's why I'm just not that sure we really can characterize this that well yet.   The one additional point I would make about KEYNOTE-789 and the potential role of immunotherapy is that some experts in thoracic oncology and general oncologists alike may prefer to introduce chemotherapy at a time of progression, but keep the osimertinib going, maybe particularly for patients with brain metastases, whether current or a history of them, where we really feel that the osimertinib adds a critical component to CNS control. We don't want to ever give osimertinib or probably other EGFR TKIs concurrently with immunotherapy. So that's just a factor that we'd really want to consider when we're prioritizing where to fit in immunotherapy, if at all.  Dr. Vamsi Velcheti: Thank you, Jack. And let's move on to the next abstract, Abstract 9002. This is a pivotal study of results from the sunvozertinib, which is an EGFR exon 20 insertion site mutation drug. There's some very promising data. Jack, how do you feel this study is going to influence practice?  Dr. Jack West: Well, this is not an agent we have access to broadly yet, but I was quite impressed by it overall. I didn't mention it. We talked about it in the pre-ASCO discussion, and it was really one that I would mark as potentially practice-changing when we can get it. DZD 9008 or sunvozertinib is a potent inhibitor of exon 20 insertion mutations, and this was 97 patients, and the majority had had a couple of lines of prior therapy. They had to have gotten chemo, and the response rate was 60%, and it was really comparable efficacy with the different mutation subtypes.   I think that the main thing that I would want to clarify a little better in my own patient population is how well the drug is really tolerated. We talked about that there was not really much grade 3 toxicity and that's true, but diarrhea rates were 67%, even though it was grade 3 and just about 8%. But grade 2 diarrhea or grade 2 rash in patients who are on this therapy, we hope for a long time, I think is something we shouldn't minimize. And I think that particularly our mindset about toxicity needs to be different when we're talking about giving a treatment for 2 or 4 cycles and then being done with it versus something we hope we're going to be giving longitudinally. And we really don't want to minimize the potential impact on the quality of life of patients who are experiencing grade 2 rash, diarrhea, or paronychia for months and months, maybe more than a year at a time.   But that said, this is twice the response rate if not more than that of what we have already had for patients with this molecular aberration with an exon 20 insertion. So I think it's compelling and I think that it's going to be really valuable to offer to our patients. I just would like to clarify better how well patients who are actually on it are feeling when you incorporate the potentially chronic toxicity issues.  Dr. Vamsi Velcheti: Thank you, Jack. And let's move on to the last abstract. This the LUNAR study, LBA9005. This is a positive phase 3 study that looked at tumor-treating fields or TTF therapy with standard of care treatments in metastatic non-small-cell lung cancer following platinum failure. This has been talked about a lot at ASCO, and Jack I'm eager to hear your key takeaways about this study.  Dr. Jack West: Well, we knew from a press release several months ago, I think back in February, that there was a significant improvement in overall survival with the addition of tumor-treated fields. Again, this concept that electric fields can lead to antimitotic effect and potentially downstream induction of immunogenic cell death and enhanced immune response, that's at least the concept. And it's of course established, has utility in patients with glioblastoma, although kind of, I would say underutilized because it can be cumbersome. And I think that's one of the things we need to factor in is that this is not the easiest approach to pursue.   But we don't have that many therapies that improve overall survival significantly in previously treated patients with non-small cell lung cancer. So, I think there's good reason to focus on this and ask how beneficial it is. It was notable, it was pretty much an even split of patients enrolled on the trial, 276 patients total, but about half had gotten chemo but not gotten immunotherapy before. And then the other half, I would say the clear majority, had gotten immunotherapy as well as chemo and got docetaxel-based treatment.     And the overall survival benefit was significant for the intent to treat total population with a hazard ratio of 0.74 and a difference in 3-year survival of 18% favoring the addition of tumor-treating fields on the chest versus 7% in the patients who didn't. It really seemed to separate between the patients who had not had an immune checkpoint inhibitor and got tumor-treating fields with the checkpoint inhibitor where the hazard ratio is 0.63 and those who got tumor-treating fields with docetaxel where the hazard ratio was 0.81. So it really wasn't significant in this population.  Toxicity, no real surprises compared to what we already knew about tumor-treating fields. Mostly dermatitis, but I would say that one of the kind of unmeasured issues is that this is a device that people have to wear on their chest carrying a battery pack with them all day long. It's essentially all the waking day, and so I think that's at least cumbersome. I wouldn't call it prohibitive, but it's a challenge. And I think we need to really ask whether the juice is worth the squeeze, whether the benefit is that compelling. And I question that when we're talking about an agent that doesn't significantly move the needle against docetaxel alone.   Again, this is a population where in the U.S. we have ramucirumab to add to docetaxel. Not everyone does that. It's not uniform, but that has a statistically significant, though modest survival benefit associated with that. We don't do better than that with tumor treating fields. And so, I think that this is an option that merits discussion and some patients may opt for it, but I suspect that most of my patients would not find the absolute difference to be that compelling for the challenges it incurs. I don't know what your perspective is here.  Dr. Vamsi Velcheti: I completely agree, Jack. And I think the study design and just the fact that the standard of care has changed over the last 5, actually 6 years since the study has been open. And I'm not really so sure I could really make much sense of the data in terms of the standard of care combination with TTF providing more benefit. And I think there are more questions than answers here and I'm not so sure which populations would benefit the most. And I think, I hate to say this, but this is a nice proof of concept. I hate to say this because it's a phase 3 study and it's a positive phase 3 study, but it's clinical relevance with the current standard of care, I think, I'm not really sure how much of an impact this would really have.    Well, Jack, I've really enjoyed speaking with you about these key advances in lung cancer that were featured at the 2023 ASCO Annual Meeting. Our listeners will find links to all the studies discussed today in the transcript of this episode. Thank you so much, Jack, for joining us today.  Dr. Jack West: Always a pleasure. Thanks so much.  Dr. Vamsi Velcheti: And just like that, we've reached the end of another enriching episode. But remember, like all good things, this too must come to an end, but only until we meet again. We really would like your feedback on the podcast. If you enjoyed the podcast, please rate, review and subscribe wherever you get your podcasts.  Disclaimer:    The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Follow today's speakers:   Dr. Vamsidhar Velcheti   @VamsiVelcheti   Dr. H. Jack West   @JackWestMD   Follow ASCO on social media:    @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn      Disclosures:    Dr. Vamsidhar 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. Jack West:   Honoraria: AstraZeneca, Genentech/Roche, Merck, Takeda, Mirati, Regneron, Amgen, Abbvie   Consulting or Advisory Role: AstraZeneca, Genentech/Roche, Merck, Takeda, Mirati Therapeutics, Regneron, Amgen, Abbvie, Summit Therapeutics   Speakers' Bureau: Takeda, Merck, AstraZeneca        

Year in Review: Clinical Investigator Perspectives on the Most Relevant New Data Sets and Advances in Immunotherapy and Other Nontargeted Approaches for Lung Cancer — Faculty Presentation 1: Management of Metastatic Non-Small Cell Lung Cancer (NSCLC) without an Actionable Mutation — Dr Heather Wakelee CME information and select publications

Featuring perspectives from Drs Luis Paz-Ares and Heather Wakelee, including the following topics: Introduction: Looking Back at Immuno-oncology Therapies (0:00) Metastatic Disease (7:46) Localized Non-Small Cell Lung Cancer (42:16) Small Cell Lung Cancer (59:48) CME information and select publications

Proceedings from our Year in Review webinar on immunotherapy and other nontargeted approaches for lung cancer. Featuring perspectives from Drs Luis Paz-Ares and Heather Wakelee, moderated by Dr Neil Love.

This episode of Lung Cancer Considered covers the recently completed European Lung Cancer Congress held in Copenhagen. Host Dr. Stephen Liu, Dr. Heather Wakelee and Dr. Paul Van Schil discuss the important research presented at the meeting.

With more than 10 known driver mutations in non-small cell lung cancer (NSCLC), testing is ever more critical, says Heather Wakelee, MD, division chief of medical oncology at Stanford University and president of the International Association for the Study of Lung Cancer. Listen as she and Peer-Spectives host Bob Figlin, MD, the Steven Spielberg Family Chair in Hematology Oncology at Cedars-Sinai Cancer, talk about how she manages patients with metastatic disease or those who need adjuvant treatment, when she starts targeted therapy or immunotherapy, and more. “We can drastically change the course of disease for a patient by giving them the appropriate targeted treatment. So that testing is so critical,” Dr. Wakelee said.

Treatment options are expanding quickly in early non-small cell lung cancer. Listen as Heather Wakelee, MD, division chief of Medical Oncology at Stanford University and president of the  International Association for the Study of Lung Cancer, describes how she's using new agents and incorporating trial findings into practice. She and host Bob Figlin, MD, the Steven Spielberg Family Chair in Hematology Oncology at Cedars-Sinai Cancer, explore the growing roles for neo- and adjuvant therapy and how to select patients for each therapeutic approach.

Featuring an interview with Dr Heather Wakelee, including the following topics: Similarities and differences in the efficacy of neoadjuvant and adjuvant immunotherapies for localized non-small cell lung cancer (NSCLC) (0:00) Available data on the treatment of patients whose disease relapses on or after adjuvant immunotherapy (6:15) Activity of immunotherapy in patients whose tumors are EGFR mutated (10:29) Case: A woman in her mid 70s with EGFR-mutated NSCLC in her right lung (14:49) Case: A woman in her early 60s with a smoking history and a 4-cm right lower lobe lesion (24:17) Case: A man in his mid 50s with a smoking history and a left upper lobe mass with high PD-L1 expression (28:04) Optimal treatment of localized NSCLC in patients who have alterations in RET, BRAF and ALK (33:08) Importance of primary care doctors screening their patients for lung cancer (37:03) CME information and select publications

Featuring a slide presentation and related discussion from Dr Heather Wakelee, including the following topics: Key efficacy and safety data with belantamab mafodotin for multiple myeloma (MM) (0:00) Guidelines for the prevention and management of keratopathy in patients receiving belantamab mafodotin (3:46) Belantamab mafodotin in combination with pomalidomide; recent data and ongoing trials with BCMA-targeted bispecific antibodies (7:30) BCMA-targeted CAR (chimeric antigen receptor) T-cell therapies under evaluation for MM (17:07) CME information and select publications

Dr Heather Wakelee from Stanford Cancer Institute in Palo Alto, California, discusses the management of localized non-small cell lung cancer. CME information and select publications here (http://www.researchtopractice.com/OncologyTodayLocalizedNSCLC22).

Featuring a discussion on the management of localized non-small cell lung cancer with Dr Heather Wakelee, moderated by Dr Neil Love.

It's Day 3 at the IASLC 2022 World Conference on Lung Cancer! Dr. Narjust Florez hosts pivotal researchers Dr. Enriqueta Felip, Dr. Mariano Provencio, and Dr. Rachael Murray to discuss their top-rated studies. IASLC President Dr. Heather Wakelee also joins in to give insight on how the committee selected these high-ranked abstracts for this year's Presidential Symposium.

Featuring perspectives from Drs Justin Gainor, Corey Langer, Luis Paz‑Ares, Heather Wakelee, Jared Weiss and Helena Yu, including the following topics: Introduction (0:00) Incorporation of immunotherapeutic strategies into the management of nonmetastatic non-small cell lung cancer (NSCLC) — Heather Wakelee, MD (3:18) Contemporary treatment for localized and metastatic NSCLC with EGFR mutations — Helena Yu, MD (33:46) Research advances shaping the current and future treatment of metastatic NSCLC with ALK rearrangements, ROS1 rearrangements or RET fusions — Justin F Gainor, MD (58:03) Targeting alterations in MET, HER2, KRAS and other oncogenes in NSCLC — Jared Weiss, MD (1:19:24) Current and future management of metastatic NSCLC without a targetable tumor mutation — Corey J Langer, MD (1:42:57) Current treatment paradigm for small cell lung cancer — Luis Paz-Ares, MD, PhD (2:07:58) CME information and select publications

Proceedings from a live webinar held during the IASLC 2021 World Conference on Lung Cancer, featuring a discussion on recent data on the management of localized non-small cell lung cancer. Featuring perspectives from Drs Edward B Garon, Harvey I Pass and Heather Wakelee, moderated by Dr Neil Love.

Featuring perspectives from Drs Edward Garon, Jarushka Naidoo, Harvey Pass and Heather Wakelee, including the following topics: Immunotherapy in Surgically Resectable Non-Small Cell Lung Cancer (NSCLC) Introduction: Tumor board discussions since ASCO 2021 (0:00) Case: A woman in her early 60s with Stage IIA lung adenocarcinoma — PD-L1-negative, pan-wild type (8:00) Case: A man in his mid-50s with Stage IIA squamous NSCLC — PD-L1 15% (22:44) Case: A man in his early 90s with Stage IB lung adenocarcinoma — PD-L1 10% (31:47) Key relevant data sets (39:07) Adjuvant Treatment of NSCLC with a Driver Mutation Case: A man in his late 60s with Stage III lung adenocarcinoma — PD-L1

A special audio program developed from a series of webinars held in conjunction with the 2021 ASCO Annual Meeting. Featuring perspectives from Drs Mark Awad, David R Spigel and Heather Wakelee.

Featuring perspectives from Drs Mark Awad, David R Spigel and Heather Wakelee, including the following topis: Immunotherapy in the (Neo)Adjuvant Setting Introduction (0:00) Case: A woman in her mid-60s with adenocarcinoma of the lung — PD-L1 of 0 — Sulfi Ibrahim, MD (1:39) Key relevant data sets (11:36) First-Line Treatment of Metastatic Non-Small Cell Lung Cancer (NSCLC) without a Targetable Tumor Mutation Case: A woman in her mid-60s with adenocarcinoma of the lung — PD-L1 of 0 (continued) — Dr Ibrahim (16:34) Case: A woman in her mid-60s with metastatic squamous cell carcinoma of the lung — PD-L1 75% — Margaret Deutsch, MD (22:42) Case: A woman in her mid-60s with metastatic adenocarcinoma of the lung and brain metastases — PD-L1 90% — Joseph Martins, MD (25:44) Case: A man in his early 70s with recurrent metastatic adenocarcinoma of the lung — TP53 and KRAS G12A mutations — Raymond Lobins, DO (30:05) Case: A man in his mid-60s with metastatic adenocarcinoma of the lung and active hepatitis C — Maria Regina Flores, MD (35:31) Case: A man in his mid-70s with metastatic adenocarcinoma of the lung — PD-L1 1% — Dr Ibrahim (37:42) Current Treatment Paradigm for Small Cell Lung Cancer (SCLC) Case: A man in his late 50s with extensive-stage SCLC — Rohit Gosain, MD (47:41) Case: A woman in her mid-60s with limited-stage SCLC — Ranju Gupta, MD (55:33) CME information and select publications

Featuring slide presentations and related discussion from Drs Mark Awad, David R Spigel and Heather Wakelee, including the following topics: Current and Potential Role of Immune Checkpoint Inhibition in the Management of Nonmetastatic Non-Small Cell Lung Cancer (NSCLC) — Heather Wakelee, MD (0:00) First-Line Management of Metastatic NSCLC without a Targetable Tumor Mutation — David R Spigel, MD (54:19) Current Treatment Paradigm for Small Cell Lung Cancer — Mark Awad, MD, PhD (1:53:04) CME information and select publications  

In this episode of Lung Cancer Considered , Dr. Heather Wakelee and Dr. Paul Van Schil join hosts Dr. Narjust Duma and Dr. Stephen Liu to discuss priorities and initiatives for IASLC in the 2021-22 year. Dr. Wakelee takes the reins as President of the IASLC this month during WCLC, the second woman to achieve this honor. Dr. Van Schil begins his term as President-Elect of the IASLC during WCLC, too.

Dr. Stephen Liu, associate professor of medicine and director of Thoracic Oncology and Developmental Therapeutics at the Georgetown Lombardi Comprehensive Cancer Center, highlights key abstracts in lung cancer featured at the 2021 ASCO Annual Meeting.   Transcript:  ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Stephen Liu. He is an associate professor of medicine and the director of thoracic oncology and developmental therapeutics at the Georgetown Lombardi Comprehensive Cancer Center. Dr. Liu joins me to highlight advances in lung cancer featured at the 2021 ASCO Annual Meeting. Dr. Liu has served in a consulting or advisory role for Genentech, Pfizer, and AstraZeneca, among other organizations. His full disclosures and those relating to all episodes of the podcast are available on our transcripts at ASCO.org/podcasts. Dr. Liu, it's great to have you on the podcast today. Dr. Stephen Liu: Thanks for having me. ASCO Daily News: Dr. Liu, a lot of people were talking about the IMpower010 study during the annual meeting. That's abstract 8500, an interim analysis that showed really promising results for patients with resected non-small cell lung cancer. Can you tell us about this practice-changing study? Dr. Stephen Liu: Well, IMpower010 was a global randomized phase III trial, and I think this really was one of the highlights of the ASCO Annual Meeting from a lung cancer standpoint. As a reminder, our current standard of care is cisplatin-based chemotherapy for patients with resected stage II to III non-small cell lung cancer and for select patients with stage IB. We know from decades of experienced multiple phase III trials, large meta-analyses, that the risk of recurrence is quite high for resected stage II/III lung cancer. And the use of up to four cycles of cisplatin-based chemotherapy does lead to an improvement in survival, and that's our standard of care. That survival improvement, however, is modest, with an absolute improvement and 5-year survival of about 5%. And so we've been trying to improve outcomes in this setting for quite some time. We know from last year's ASCO that the subset of patients whose tumor harbors an EGFR mutation received some benefit from disease-free survival with the use of adjuvant osimertinib. IMpower010 presented at this year's ASCO by Dr. Heather Wakelee looks at the use of immunotherapy as a complementary adjuvant therapy. And we knew from press release that this study had met its primary endpoint. This was our first chance to look at the data first-hand and really see how it would impact practice. And I think the data were quite impressive. It's a fairly simple design. This study included patients with completely resected stage IB to IIIA non-small cell lung cancer, either histology. Note that this used AJCC version 7, and so the stage IB that were included had a size of at least four centimeters, and that's the subset that seems to derive the most benefit from chemotherapy. Now patients received cisplatin-based chemotherapy one to four cycles first. And those who received at least one cycle of chemotherapy were then randomly assigned 1 to 1 to receive 1 year of atezolizumab, PD-L1 inhibitor, or best supportive care. This was a large study, over 1,000 patients randomly assigned. It began enrollment in 2014. So it did include some EGFR and some ALK when maybe we didn't know quite as much about including those patients in these studies, but the EGFR was about 12%, the ALK was 3%. Some were unknown EGFR and ALK status, but these were likely the squamous histology, as those numbers line up. The PD-L1 testing, importantly, was done by the VENTANA SP263 assay, looking at tumor cell expression only, which is a fairly straightforward assay. And what we saw after a median follow up of almost 3 years was that in the primary high-risk population stage II to IIIA resected non-small cell lung cancer with the PD-L1 expression of at least 1%, the use of adjuvant atezolizumab significantly improved disease-free survival. And the hazard ratio there was 0.66. If we look at the 2-year disease-free survival (DFS) rate, it improved from 61% with best supportive care to 75%, and at 3-year DFS from 48% to 60%. So an improvement in the 3-year DFS rate and a hazard ratio of 0.66. The fourth plot showed that signal was greater in node-positive. As expected, no signal in that ALK subset, though it was small. But this is a pretty substantial improvement in disease-free survival. When we look at these Kaplan-Meier curves, they split immediately, really right at the first scan. And when we look at a study like this, this phase III trial, it reminds us how poor our current standard is; how many patients do suffer relapse and recurrence and death from this potentially curable cancer. Atezolizumab clearly improving outcomes in this subset. We then saw analyses of the resected stage II to III across PD-L1 strata, so positive and negative. And there the hazard ratio, as expected, less impressive, 0.79. If we look at the forest plot there, the hazard ratio for PD-L1 high, using that 50% cutoff we're used to, was substantial at 0.43. So overall, the DFS and PD-L1 positive 0.66 and the PD-L1 high 0.43. So no report on the PD-L1 low, which is what we're waiting for, that one at 49%, presumably not as impressive as 0.66. And we'll wait for those data to come out. But PD-L1 positive, a clear benefit. PD-L1 high, a substantial benefit. That's really where the formal analyses stopped. The stage IB to IIIA overall population was too immature for analysis, and overall survival was not yet formally tested. This will take a few years to breathe out. They did provide an early look at overall survival. And in that stage II to IIIA PD-L1 positive, there was the right trend, with a hazard ratio of 0.77, though not statistically significant. We did see these curves start to come apart at about 12 to 18 months, which is what you would expect if this study ultimately would lead out to be positive. We do want to wait for OS results. But one has to wonder, is a DFS benefit this substantial enough to change practice? And atezolizumab not yet approved in this setting, but the trial did meet its primary endpoint. And to me, for PD-L1 positive, and certainly for PD-L1 high, I do think these data aren't practice- changing. ASCO Daily News: Absolutely. Well, another trial that attracted a lot of attention was the CheckMate-816 trial. That's Abstract 8503. What can you tell us about the surgical outcome data reported in CheckMate-816? Dr. Stephen Liu: So CheckMate- 816 was a randomized phase III trial that looked at neoadjuvant therapy. So this also focused on resectable lung cancer. This is an area where we hope for cure, but for some of the more advanced stages, we don't necessarily expect it. Much room for improvement. We saw the IMpower010 data showing adjuvant immunotherapy improved DFS. Here we're looking at the neoadjuvant space. And at AACR in 2021, Dr. Patrick Forde presented some of the early PCR results. And that showed the pathologic complete response rates with neoadjuvant nivolumab plus chemotherapy for three cycles was superior to chemotherapy alone for three cycles. So the addition of nivolumab to chemotherapy improved the pathological CR rate from 2% to 24%. Really astounding. What Dr. Jonathan Spicer presented at ASCO 2021 were the surgical outcomes from that study. And we see that adding immunotherapy to chemotherapy significantly improves the pathologic CR rate. Does it come at a cost? Does it lead to more surgical complications? This is always a concern with neoadjuvant therapies. We've got someone in our clinic with a resectable lung cancer. If we mismanage that patient, we may lose the window for resection. So we always worry about delayed surgeries, canceled surgeries, more complicated surgeries. There have anecdotally been reports of increased perihilar fibrosis after neoadjuvant immunotherapy. Wouldn't that lead to longer, more complicated surgeries? And what we saw, frankly, was a bit surprising, for me. Surgery consistently easier, better in the experimental arm really across the board. The rates of going to surgery, completing surgery, 83% with nivolumab/chemotherapy, versus 75% with chemotherapy. So more patients going to surgery, fewer canceled surgeries. If we look at the type of surgery, minimally invasive surgery rates 30% with nivolumab/chemotherapy, [and] 22% with chemotherapy alone. Conversion to open thoracotomy was more common in the chemotherapy alone at 16%, the additional nivolumab 11%. And the complete R0 resection was achieved in 83% with nivolumab/chemotherapy, 78% with chemotherapy alone. Adverse events delayed surgery in six patients getting nivolumab and chemotherapy. It's important to watch that. But it was nine patients in getting chemotherapy alone. And if we look at the duration of surgery, and certainly there are many confounders in a statistic like this, but the surgery was shorter with nivolumab, certainly not lengthening the surgery. 184 minutes for nivolumab/chemotherapy, 217 [minutes] with chemotherapy alone. So these data are very reassuring to someone with a potentially resectable cancer. And I think that when I take a step back and look, maybe these results do make sense. Maybe this is what I should have expected. If we give a treatment that is more effective, that is a higher response rate, it works better. Those patients are less likely to have progressive disease, and the surgery should be more straightforward if there's less cancer to resect. So the CheckMate-816 surgical data, we've been waiting for this shoe to drop, and it was very reassuring. Perioperative immunotherapy is going to be an important part in the management of stage II/III non-small cell lung cancer in the years to come. Now going forward, we'll need to compare these adjuvant and neoadjuvant approaches and the relative merits of either strategy, but these results, I thought, were very reassuring. ASCO Daily News: Excellent. Well, moving on to the PACIFIC trial, Abstract 8511, this study reported improvements in 5-year overall survival and progression-free survival for unresectable stage III non-small cell lung cancer. What are your takeaways from this study? Dr. Stephen Liu: Sure. The PACIFIC study is a randomized phase III trial that's really set our standard of care for unresectable stage III locally advanced non-small cell lung cancer. This is a group where our standard of care, historically, has been concurrent chemoradiation, with the goal of cure, though, unfortunately, not necessarily the expectation, with recurrence rates quite high. We saw years ago the addition of 1 year of durvalumab improved progression-free survival, then ultimately improved overall survival compared to placebo. This was a fairly straightforward study. It enrolled unresectable stage III non--small cell lung cancer after chemoradiation, who did not have evidence of progression after completing therapy, to receive 1 year of durvalumab or placebo, a 2 to 1 randomization. The results markedly positive, leading to U.S. Food and Drug Administration (FDA) approval and really our new standard of care. These are long-term survival data, and it was presented by Dr. David Spigel. These are really important. Immunotherapy, the whole appeal of the strategy is the durability, the induction of memory T cells, meaningful long-term survival. Will this increase the rate of cure really is what we're going for. And when we saw the survival benefit with durvalumab, we knew that we were curing more patients. Long-term follow up is important to make sure that we don't have late recurrences, that we really are curing and not just delaying a recurrence for some patients. And in this analysis, with a 5-year follow up, we see durvalumab improve the median survival from 29 months with chemoradiation alone to 48 months with the addition of durvalumab. That's a hazard ratio of 0.72, 28% reduction in the risk of death, pretty substantial. That 5-year survival rate was 43% versus 33%. And importantly, these were very similar to the 4-year data that were presented by Dr. Corinne Faivre-Finn at World Conference in Lung Cancer, really very little drop off between year 4 and 5. And we refer to that as flattening of the tail, where the events are early, and at some point, they kind of stop happening. It's really what we want to see. While survival is what we hone in on, in an abstract like this, we also need to pay attention to progression-free survival (PFS). And the PFS rate at 5 years was 33% with durvalumab, versus 19% with chemoradiation alone. So 33% with no evidence of progression at 5 years. And if you are cured from lung cancer, then you can't have progression. So one in the three patients with no progression at 5 years, I think, is very reassuring, that PFS hazard ratio of 0.55. So prior to ASCO21, durvalumab was our standard of care. Now we just have longer term follow up to really solidify that choice. These are important data for patients and families to set expectations right, but our clear standard. Still, though, room for improvement in that 5-year PFS rate of 33%. We would like to see that higher, and ongoing strategies hopefully will help push that up. ASCO Daily News: Excellent. Some great survival data in the PACIFIC trial. Well, Abstract 9007 sparked a lot of interest as well. This is an expansion study of patritumab/deruxtecan in patients with EGFR-mutant non-small cell lung cancer. That's a difficult drug to pronounce, so I'm sure you'll do a better job. What can you tell us about this? Dr. Stephen Liu: Well, yeah, all these antibody drug conjugates do have tricky names, and so they are kind of fun to say. So patritumab/deruxtecan is a HER3 antibody drug conjugate. I suspect it will be better known as HER3-DXd, a little easier off the tongue. This was a study that looked at this agent in patients with EGFR-mutant non--small cell lung cancer after TKI therapy. And when we turn our attention to targeted agents, we have really transformative drugs with very wide therapeutic windows, little toxicity, very high efficacy, [and are] really game changers in patients with driver positive non--small cell lung cancer. But as we know, these treatments aren't cures. And we do expect resistance to osimertinib. The third generation TKI has been pretty heterogeneous. And once patients progress in osimertinib, the next standard therapy really is chemotherapy. And there's a bit of a drop off, with more toxicity, [and] less efficacy overall. So this remains an unmet need. Many studies are looking at different strategies there. We've seen the addition of MET inhibitors if MET is amplified for certain subtypes, RET, BRAF, for example, the addition of the targeted agents. This study, Abstract 9007 presented by Dr. Pasi Janne, looked at the HER3-DXd antibody drug conjugate. So patritumab/deruxtecan has a monoclonal antibody targeting HER3, a proprietary linker, and then a topoisomerase 1 warhead. And this was a phase I study that looked at 57 patients with EGFR-mutant lung cancer after TKI therapy mostly, but 90% were coming off of osimertinib. And what we saw, I thought, was very encouraging. This is a small, early study. These are very selective patients. But the response rate here almost 40%, disease control rate 72%, and the median progression-free survival with monotherapy of patritumab/deruxtecan was 8.2 months. These numbers may change as the studies get larger, but there's a clear signal of efficacy for patients who'd received chemotherapy before and then moved on to patritumab/deruxtecan. The response rate didn't really drop off, 37%. So even those that were more heavily pretreated, we're seeing a clear signal with response rates that really are higher than chemotherapy. What was, I think, most important, we saw efficacy of patritumab/deruxtecan across multiple different mechanisms of resistance. And so it wasn't one biomarker select. It really was active, very versatile agent. And really, I think that's what we need. While biomarker-driven resistance will be something we always hone in on and try to focus, we do need something that's much more versatile for rapid implementation. And this is having a lot of potential. [It was] very well tolerated. If we look at treatment-emergent adverse events, only one person stopped from a TEAE. Only 4% stopped due to TEAEs, so very well tolerated treatment. Response was also durable. One response listed was after 4 years of therapy, and so the potential for long-term disease control, long-term responses. So clearly an active drug. This is an area where we need a lot of drug development. Well tolerated, only 4% stopping due to adverse events and a nice signal of activity. Our next steps will be to make this a larger study to look in more patients to really hone in on the mechanisms and where this really is working. Can we widen that therapeutic index? And can we look at combinations? Is there a role to continue TKI with this, maybe for better CNS coverage or activity? That's what we'll see in the years to come. ASCO Daily News: Excellent. Well I'd like to ask you about a trial that you were involved in, the ARROW trial, Abstract 9089. Can you tell us about this impactful study? Dr. Stephen Liu: Yeah, sure. The ARROW trial is a study that I've been a co-investigator on for many years. This was presented by Dr. Giuseppe Curigliano. And this looks at a RET inhibitor called pralsetinib, originally when we first got involved called BLU-667. RET fusions are present in about 1% of non- small cell lung cancer. These are important events, because we know from other studies, such as the immunotarget registry led by Julien Mazieres,  that RET-positive lung cancers don't seem to respond as well to immunotherapy. However, in the past, the kinase inhibitors, the targeted agents we had the targeted RET, weren't very good. They had response rates around 30%, 40%, a lot of toxicity. These are drugs like vandetanib, cabozantinib. With the introduction of selective RET inhibitors, we've seen striking efficacy and much better tolerability. And we now have two approved RET inhibitors in this space--selpercatinib and pralsetinib--both receiving FDA accelerated approval based on their respective single arm studies. What we saw at ASCO 2021 from Dr. Curigliano was an update on the RET fusion positive lung cohort of ARROW. Again, this was a phase I/II trial looking at pralsetinib given at a dose of 400 milligrams by mouth once daily. We look at the patients with RET fusion-positive lung cancer. Now we just have longer follow up and more patients. And overall, the cohort exceeded 200 patients, so 216 patients for a pretty rare driver. And the response rate, 69%, very durable. The duration of response, 22 months. So really solidifying the efficacy and confirming the role in patients with RET fusion-positive lung cancer. If we break those data down a little bit, patients who had prior chemotherapy, which was 125 patients, response rate was 62%. The disease control rate, 91%. These responses are quick. The median time to responses is 1.8 months, so really that first scan. And that's what we see with targeted therapy. And we look at these waterfall plots, and I encourage you to take a peek at that. It's exactly what we want to see, the vast majority of patients, almost all patients, with some reduction and some with a quite substantial reduction. Again, the disease control rate after chemo was 91%. So really, the waterfall plot has that look that we seek for effective targeted therapy. The outcomes were even better in the first-line setting. Response rate originally 79% as first-line therapy. But the way the trial was originally written, it only included frontline patients who weren't eligible for chemotherapy for whatever reason. So that's going to be a more selective cohort. That was changed with an amendment. And once that was removed for people that were eligible for whatever frontline therapy you wanted to give, really our real world first line cohort, the response rate was 88%, disease control rate of 96%. So to think of a response rate in almost 90% of patients really gives us that confidence we want when we have a driver that we detect when we start a new agent. We're very confident that we're going to see efficacy in these drugs, very well tolerated, very few patients stopping due to a adverse event. A disease control rate of 96% in that first-line setting gives me the confidence to really use this in the first-line setting. ASCO Daily News: Absolutely. Well, as you know, the Annual Meeting this year focused on equity in cancer care. And there were a number of studies presented in the lung cancer space. I just wanted to get your thoughts on how this issue was addressed at the Annual Meeting in the lung cancer setting. I'm thinking of Abstract 9005 that looked at racial disparities. What are your thoughts on this issue? Dr. Stephen Liu: Yeah, this was an important abstract, I think. And the theme that Dr. Lori Pierce set of equity really was met by several different abstracts and was a recurrent focus for many important and really overdue discussions. Abstract 9005 was presented by Dr. Debora Bruno, and this really looked at disparities in biomarker testing. And we just talked about advances for EGFR-mutant lung cancer for RET fusion-positive non--mall cell lung cancer. We have many, many more, but we can only offer these agents if we know the target is present. And if we don't do proper biomarker testing, our care will not be optimal. If we don't know the molecular genotype of the cancer, we can't treat it properly. We are just guessing, and we're much more likely to deliver an ineffective therapy. We are potentially making subsequent therapies more dangerous. Knowing the right biomarker is critical to the proper management of non-small cell lung cancer. And if we don't have that, the outcomes will not be as good. The testing really is critical for the management of lung cancer. And what we saw from this abstract was there are disparities in how patients with non-small cell lung cancer are being tested, which simply isn't acceptable. This was a retrospective analysis that looked at Flatiron data, recent data, 2017 to 2020, a large data set, almost 15,000 patients with non-small cell lung cancer. Demographics were 66% white, 9% Black. If we look at biomarker testing specifically, patients who were Black were less likely to be tested, less likely to have proper biomarker testing, 73% versus 76%, less likely to have full next generation sequencing with a 10% difference, and less likely to get tested early. We know that testing really influences treatment from the jump right away. And if we don't have that information, our outcomes won't be as good. Our Black patients weren't being tested properly, weren't being tested in a timely manner. And more data showed that clinical trial participation was also decreased among Black patients, 4% involvement for white patients, 2% with Black patients. And these were actually very similar to what we saw in Abstract 9001 that was presented by Dr. Akinboro from the FDA. And that looked at patients who'd received chemoimmunotherapy. This was a pooled analysis looking at different PD-L1 cohorts. And what was noted on the demographics is that in the phase III registrational landmark studies, Black patients only represented about 2% of patients there as well. So strikingly similar numbers and a gross under-representation. It really is inexcusable and something we need to address. And we need to correct, because this is showing that our care is simply not up to par.  Trial participation is how we move the field, but many cases, especially in lung cancer, a field that moves so quickly, a clinical trial often represents the best possible option. And Black patients simply aren't enrolling in studies. And I think some of the disparities in clinical trial participation likely reflect some of the disparities in clinical trialists. And I think that if we continue to improve diversity in our workforce, in our oncology subspecialty, that'll be an important step into rectifying this. But this is something we need to look at critically. We need to assess all of our processes and think how we can do better today, and not tomorrow. ASCO Daily News: Absolutely. Thank you so much, Dr. Liu, for highlighting these really critical points and sharing your valuable insight on all of these impactful studies in lung cancer. Thank you so much. Dr. Stephen Liu: My pleasure. Thanks for having me. ASCO Daily News: And thank you to our listeners for joining us today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. Stephen Liu Consulting or Advisory Role: Genentech, Pfizer, Lilly, Bristol-Myers Squibb, AstraZeneca, Takeda, Regeneron, G1 Therapeutics, Guardant Health, Janssen Oncology, MSD Oncology, Jazz Pharmaceuticals, Blueprint Medicines, Inivata, PharmaMar, Daiichi Sankyo/UCB Japan, BeiGene, Amgen, Turning Point Therapeutics, Elevation Oncology, and Novartis Research Funding (institution): Genentech/Roche, Pfizer, Bayer, Merck, AstraZeneca, Blueprint Medicines, Lilly, Rain Therapeutics, Alkermes, Bristol-Myers Squibb, Turning Point Therapeutics, RAPT, Merus, Elevation Oncology, and Erasca, Inc Travel, Accommodations, Expenses: AstraZeneca, Roche/Genentech, and MSD Oncology   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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

The American Society of Clinical Oncology meeting just concluded and Lung Cancer Considered has a summary of the meeting, with a unique lung cancer focus. Tune in as host Stephen Liu and guests Dr. Alfredo Addeo and Dr. Heather Wakelee discuss key findings from ASCO 2021.

Dr. Heather Wakelee joins GRACE to discuss treatment options for a metastatic non small cell lung cancer diagnosis.

Proceedings from a daylong symposium hosted in partnership with North Carolina Oncology Association and South Carolina Oncology Society, featuring key clinical presentations and papers in acute myeloid leukemia and myelodysplastic syndromes, breast cancer, chronic lymphocytic leukemia and lymphomas, gastrointestinal cancers, genitourinary cancers, lung cancer and multiple myeloma. Featuring perspectives from Drs Courtney D DiNardo, Robert Dreicer, Justin F Gainor, Sara Hurvitz, Ian E Krop, John M Pagel, Alexander Perl, Daniel P Petrylak, Philip A Philip, Paul G Richardson, Mitchell R Smith, Prof Eric Van Cutsem and Drs Peter Voorhees and Heather Wakelee, moderated by Dr Neil Love.

Proceedings from a daylong symposium hosted in partnership with North Carolina Oncology Association and South Carolina Oncology Society, featuring key clinical presentations and papers in acute myeloid leukemia and myelodysplastic syndromes, breast cancer, chronic lymphocytic leukemia and lymphomas, gastrointestinal cancers, genitourinary cancers, lung cancer and multiple myeloma. Featuring perspectives from Drs Courtney D DiNardo, Robert Dreicer, Justin F Gainor, Sara Hurvitz, Ian E Krop, John M Pagel, Alexander Perl, Daniel P Petrylak, Philip A Philip, Paul G Richardson, Mitchell R Smith, Prof Eric Van Cutsem and Drs Peter Voorhees and Heather Wakelee, moderated by Dr Neil Love.

Proceedings from a daylong symposium hosted in partnership with North Carolina Oncology Association and South Carolina Oncology Society, featuring key clinical presentations and papers in acute myeloid leukemia and myelodysplastic syndromes, breast cancer, chronic lymphocytic leukemia and lymphomas, gastrointestinal cancers, genitourinary cancers, lung cancer and multiple myeloma. Featuring perspectives from Drs Courtney D DiNardo, Robert Dreicer, Justin F Gainor, Sara Hurvitz, Ian E Krop, John M Pagel, Alexander Perl, Daniel P Petrylak, Philip A Philip, Paul G Richardson, Mitchell R Smith, Prof Eric Van Cutsem and Drs Peter Voorhees and Heather Wakelee, moderated by Dr Neil Love.

Proceedings from a daylong symposium hosted in partnership with North Carolina Oncology Association and South Carolina Oncology Society, featuring key clinical presentations and papers in acute myeloid leukemia and myelodysplastic syndromes, breast cancer, chronic lymphocytic leukemia and lymphomas, gastrointestinal cancers, genitourinary cancers, lung cancer and multiple myeloma. Featuring perspectives from Drs Courtney D DiNardo, Robert Dreicer, Justin F Gainor, Sara Hurvitz, Ian E Krop, John M Pagel, Alexander Perl, Daniel P Petrylak, Philip A Philip, Paul G Richardson, Mitchell R Smith, Prof Eric Van Cutsem and Drs Peter Voorhees and Heather Wakelee, moderated by Dr Neil Love.

Proceedings from a daylong symposium hosted in partnership with North Carolina Oncology Association and South Carolina Oncology Society, featuring key clinical presentations and papers in acute myeloid leukemia and myelodysplastic syndromes, breast cancer, chronic lymphocytic leukemia and lymphomas, gastrointestinal cancers, genitourinary cancers, lung cancer and multiple myeloma. Featuring perspectives from Drs Courtney D DiNardo, Robert Dreicer, Justin F Gainor, Sara Hurvitz, Ian E Krop, John M Pagel, Alexander Perl, Daniel P Petrylak, Philip A Philip, Paul G Richardson, Mitchell R Smith, Prof Eric Van Cutsem and Drs Peter Voorhees and Heather Wakelee, moderated by Dr Neil Love.

Proceedings from a daylong symposium hosted in partnership with North Carolina Oncology Association and South Carolina Oncology Society, featuring key clinical presentations and papers in acute myeloid leukemia and myelodysplastic syndromes, breast cancer, chronic lymphocytic leukemia and lymphomas, gastrointestinal cancers, genitourinary cancers, lung cancer and multiple myeloma. Featuring perspectives from Drs Courtney D DiNardo, Robert Dreicer, Justin F Gainor, Sara Hurvitz, Ian E Krop, John M Pagel, Alexander Perl, Daniel P Petrylak, Philip A Philip, Paul G Richardson, Mitchell R Smith, Prof Eric Van Cutsem and Drs Peter Voorhees and Heather Wakelee, moderated by Dr Neil Love.

Proceedings from a daylong symposium hosted in partnership with North Carolina Oncology Association and South Carolina Oncology Society, featuring key clinical presentations and papers in acute myeloid leukemia and myelodysplastic syndromes, breast cancer, chronic lymphocytic leukemia and lymphomas, gastrointestinal cancers, genitourinary cancers, lung cancer and multiple myeloma. Featuring perspectives from Drs Courtney D DiNardo, Robert Dreicer, Justin F Gainor, Sara Hurvitz, Ian E Krop, John M Pagel, Alexander Perl, Daniel P Petrylak, Philip A Philip, Paul G Richardson, Mitchell R Smith, Prof Eric Van Cutsem and Drs Peter Voorhees and Heather Wakelee, moderated by Dr Neil Love.

Proceedings from a daylong symposium hosted in partnership with North Carolina Oncology Association and South Carolina Oncology Society, featuring key clinical presentations and papers in lung cancer. Featuring perspectives from Drs Justin F Gainor and Heather Wakelee, including the following topics: Introduction Non-Small Cell Lung Cancer (NSCLC) with an EGFR Tumor Mutation Metastatic NSCLC Harboring Other Mutations Localized or Locally Advanced NSCLC Newly Diagnosed NSCLC with No Actionable Mutation Newly Diagnosed Extensive-Stage Small Cell Lung Cancer CME information and select publications

Dr. Heather Wakelee discusses whether blood-based mutation-testing can help shape treatment decisions for advanced NSCLC.

Dr. Heather Wakelee discusses which patients should receive consolidation immunotherapy after chemo radiation for stage 3 unresectable non small cell lung cancer.

For this round of case based panel discussions, Dr. Jack West is joined by Drs. Heather Wakelee and Caroline McCoach.Dr. Wakelee is Professor of Medicine in the Division of Medicine and Oncology at Stanford University Medical Center.Dr. McCoach is Assistant Professor in the Thoracic Medical Oncology Division of the UCSF Helen Diller Comprehensive Cancer Center in San Francisco, California. In this series, the doctors discuss a series of cases related to EGFR Mutations. In this case, the discussion surrounds patient progression in a case with EGFR mutation, and what are the next steps. For more, please visit http://cancerGRACE.org/. To join the conversation, visit https://cancergrace.org/forum.

For this round of case based panel discussions, Dr. Jack West is joined by Drs. Heather Wakelee and Caroline McCoach.Dr. Wakelee is Professor of Medicine in the Division of Medicine and Oncology at Stanford University Medical Center.Dr. McCoach is Assistant Professor in the Thoracic Medical Oncology Division of the UCSF Helen Diller Comprehensive Cancer Center in San Francisco, California. In this series, the doctors discuss a series of cases related to EGFR Mutations. In this case, the discussion surrounds a case with an EGFR Mutation and High PDL1. The discussion centers around the role of immunotherapy in treatment decisions. For more, please visit http://cancerGRACE.org/. To join the conversation, visit https://cancergrace.org/forum.

For this round of case based panel discussions, Dr. Jack West is joined by Drs. Heather Wakelee and Caroline McCoach.Dr. Wakelee is Professor of Medicine in the Division of Medicine and Oncology at Stanford University Medical Center.Dr. McCoach is Assistant Professor in the Thoracic Medical Oncology Division of the UCSF Helen Diller Comprehensive Cancer Center in San Francisco, California. In this series, the doctors discuss a series of cases related to EGFR Mutations. In this case, the discussion surrounds an EGFR mutation with MET amplification. They review treatment decisions and the importance of the level of MET amplification.For more, please visit http://cancerGRACE.org/. To join the conversation, visit https://cancergrace.org/forum.

For this round of case based panel discussions, Dr. Jack West is joined by Drs. Heather Wakelee and Caroline McCoach.Dr. Wakelee is Professor of Medicine in the Division of Medicine and Oncology at Stanford University Medical Center.Dr. McCoach is Assistant Professor in the Thoracic Medical Oncology Division of the UCSF Helen Diller Comprehensive Cancer Center in San Francisco, California. In this series, the doctors discuss a series of cases related to EGFR Mutations. In this discussion they review the recommended treatment for a common EGFR mutation. For more, please visit http://cancerGRACE.org/. To join the conversation, visit https://cancergrace.org/forum.

For this round of case based panel discussions, Dr. Jack West is joined by Drs. Heather Wakelee and Caroline McCoach.Dr. Wakelee is Professor of Medicine in the Division of Medicine and Oncology at Stanford University Medical Center.Dr. McCoach is Assistant Professor in the Thoracic Medical Oncology Division of the UCSF Helen Diller Comprehensive Cancer Center in San Francisco, California. In this series, the doctors discuss a series of cases related to EGFR Mutations. In this case, the discussion surrounds an EGFR mutation treated with Tagrisso, and progression while on treatment. The doctors also discuss the role of repeat biopsy. For more, please visit http://cancerGRACE.org/. To join the conversation, visit https://cancergrace.org/forum.

For this round of case based panel discussions, Dr. Jack West is joined by Drs. Heather Wakelee and Caroline McCoach.Dr. Wakelee is Professor of Medicine in the Division of Medicine and Oncology at Stanford University Medical Center.Dr. McCoach is Assistant Professor in the Thoracic Medical Oncology Division of the UCSF Helen Diller Comprehensive Cancer Center in San Francisco, California. In this series, the doctors discuss a series of cases related to EGFR Mutations - is there a place for chemotherapy and an EGFR inhibitor concurrently or sequentially in treatment decisions?For more, please visit http://cancerGRACE.org/. To join the conversation, visit https://cancergrace.org/forum.

For this round of case based panel discussions, Dr. Jack West is joined by Drs. Heather Wakelee and Caroline McCoach.Dr. Wakelee is Professor of Medicine in the Division of Medicine and Oncology at Stanford University Medical Center.Dr. McCoach is Assistant Professor in the Thoracic Medical Oncology Division of the UCSF Helen Diller Comprehensive Cancer Center in San Francisco, California. In this series, the doctors discuss a series of cases related to EGFR Mutations - is there a place for chemotherapy and an EGFR inhibitor concurrently or sequentially in treatment decisions?For more, please visit http://cancerGRACE.org/. To join the conversation, visit https://cancergrace.org/forum.

For this round of case based panel discussions, Dr. Jack West is joined by Drs. Heather Wakelee and Caroline McCoach.Dr. Wakelee is Professor of Medicine in the Division of Medicine and Oncology at Stanford University Medical Center.Dr. McCoach is Assistant Professor in the Thoracic Medical Oncology Division of the UCSF Helen Diller Comprehensive Cancer Center in San Francisco, California. In this series, the doctors discuss a series of cases related to an EGFR mutation. In this podcast, the discussion is regarding uncommon EXON 20 mutation, suggested treatments, targeted therapy and clinical trials. For more, please visit http://cancerGRACE.org/. To join the conversation, visit https://cancergrace.org/forum.

For this round of case based panel discussions, Dr. Jack West is joined by Drs. Heather Wakelee and Caroline McCoach.Dr. Wakelee is Professor of Medicine in the Division of Medicine and Oncology at Stanford University Medical Center.Dr. McCoach is Assistant Professor in the Thoracic Medical Oncology Division of the UCSF Helen Diller Comprehensive Cancer Center in San Francisco, California. In this series, the doctors discuss a series of cases related to EGFR Mutations. For EGFR mutations and the FLAURA trial, is there a difference in data based on demographics and how can that effect treatment decisions? For more, please visit http://cancerGRACE.org/. To join the conversation, visit https://cancergrace.org/forum.