Research Highlights from the 2022 North America Conference on Lung Cancer, with Xiuning Le, MD, PhD

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests’ statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. In this podcast, Dr. Xiuning Le discusses new research on targeted therapy for non-small cell lung cancer presented at the 2022 North America Conference on Lung Cancer, held September 23-25 in Chicago, Illinois. Dr. Le is an assistant professor in the Department of Thoracic/Head and Neck Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston, Texas. She is also a 2022 Lung Cancer Advisory Panelist on the Cancer.Net Editorial Board. You can view Dr. Le’s disclosures at Cancer.Net. Dr. Le: Hi everyone. This is Xiuning Le. I'm an assistant professor here at MD Anderson in the Department of Thoracic/Head and Neck Medical Oncology department. I am a medical oncologist. I am a clinical investigator and also translational researcher. So today is a great opportunity to discuss some of the new meeting updates from 2022 North America Conference on Lung Cancer. Let me begin with the information about the meeting itself. So this conference, North America Conference on Lung Cancer, is organized by an organization called the International Association for the Study of Lung Cancer. As reflected in the name, this is an international organization for all the lung cancer researchers to get together to share our research, experience, and also patient advocates as well as patients participate in this fantastic organization. This organization also has meetings every year, including a World Lung Conference as well as the meeting we're going to talk a little bit about today, focusing on the progress we made in the North America. Therefore, it's called North America Conference on Lung Cancer. In this year's meeting, we had a very active agenda with multiple presenters from different parts of the U.S. And we also had international participants as well. We had exciting updates on some of the targeted therapy trials as well as updates from immunotherapy trials. So it was a very productive meeting. Let me start with some of the updates from the targeted therapy space. During the meeting oral presentation, there were 3 abstracts selected for oral presentations. The first talk I would briefly discuss today is an update study for ADAURA trial using osimertinib as an adjuvant therapy for resected lung cancer patients whose tumor has EGFR mutation. This was presented by Dr. Roy Herbst, key investigator on the trial from Yale Cancer Center. So ADAURA trial is a multicenter international trial taking patients whose lung cancer have EGFR classical mutation at the diagnosis, or stage 1B to 3A, and then undergoing chemotherapy as the initial adjuvant treatment. But after completion of those treatments, patients were offered opportunities to go on to the trial receiving either osimertinib for 3 years or best supportive care placebo. The primary report of this trial became available in year 2021, where the osimertinib-treated patient had a significant clinical benefit reflected as the disease-free survival was much higher in the patient population who received osimertinib. The results of the ADAURA trial led to the FDA approval of using osimertinib in the surgically resected EGFR-mutant non-small cell lung cancer. So that's the background of this year's update and presentation. Now, in the fall of 2022, after additional long follow-up, the data become more mature because although we still don't have overall survival results, we start to have 3-year disease-free survival. So in the study population, each is over 300 patients each arm, the 3-year disease-free survival rate was 84% for patients who receive osimertinib and then for placebo group is 34%. As you can see, this is a 2.5-fold significant benefit in the patient who received the treatment. The presentation was also a breakdown the patient population by their stage by different subgroup analysis across the board. The patient who received osimertinib derived benefit and then the hazard ratio remained to be between 0.2 to 0.3, depending which population we're looking at. Really, this data validated and confirmed the prior knowledge of this approach of offering adjuvant osimertinib really works and really should be offered to every single patient who qualifies for this study. One update on the subgroup analysis is the benefit for preventing brain metastasis to happen in the patients. Very impressive. We observe a hazard ratio of 0.24, meaning that if a patient goes on to osimertinib has a 4-fold benefit of not to develop brain metastasis. Overall, the conclusion of this presentation is that this data becoming more mature, and then the mature data reinforced that adjuvant osimertinib really should be the standard of care which we have been using pretty widely in the clinic. The second abstract I want to talk about is a presentation that's presented by Dr. Lyudmila Bazhenova from University of California, San Diego. So she presented a pooled updated analysis on a novel EGFR exon 20 insertion medication. And then this medication currently is under U.S. FDA evaluation with breakthrough therapy designation. The drug's chemical name is called DZD9008, and then the drug's brand name is sunvozertinib. This is a great addition to the treatment option that we already start to see for EGFR exon 20 as a new inhibitor coming at the horizon. EGFR, we now start to classify all the mutations into classical mutation versus exon 20 mutation, as we are using different targeted therapy for different patients. For EGFR exon 20 insertion, we have already 2 FDA-approved drugs. One is amivantamab, the other is mobocertinib. But we still need more options for our patients. And this new medication, DZD9008, is having a great potential of becoming the next-generation EGFR exon 20 drug, as it showed good efficacy and pretty low toxicity. So let's review the data that's presented here. In this meeting abstract, the authors combined 2 studies. One is called WU-KONG1. The other is called WU-KONG2. The first one was conducted in the U.S., and the second one was conducted in China. So there is a value of pooling different patient populations together and then not just getting the sample size greater but also understand different patient population, are they all having very similar benefit? Here the focus on analyzing the patient population that EGFR exon 20 lung cancer who have already received the chemotherapy. In the total of 71 patients analyzed here, in the subgroup of receiving 300 mg daily dose, the response rate was observed to be 40% to 45% depending on if you're using the central review system or you're using the investigator evaluation. But again, showing a very promising response. I want to put those numbers in the reference. For example, the currently FDA approved, the mobocertinib, in their population also had prior treatment. The response for mobocertinib was 28%. In the over 100 patient population, in these 71 patients, they see a 40% to 45% response. So potentially this one is having an even better efficacy really translate into clinic can be a great opportunity for the patients who had chemotherapy and needs something else. Also, we reviewed the toxicity profile. This drug is overall pretty well tolerated. We have to say that the population is relatively small. In order to truly understand toxicity, we usually want to look at the multi-hundred patients' experience, but I believe the data will mature over time. I would have to say the result here is very exciting. The third abstract I will be talking about today is presented by myself, Xiuning Le from MD Anderson. In this abstract, we evaluated tepotinib, which is a MET inhibitor, their efficacy and safety in MET amplified non-small cell lung cancer patients. As we already know, MET exon 14 skipping represents a molecular subgroup that can benefit from MET TKI, including tepotinib. But MET amplification without MET exon 14 is another patient subgroup that could potentially benefit from MET inhibition. As in those cancers, MET not using exon 14 skipping as driving events rather than amplify. So the gene makes many copies of itself, so that drives the tumor growth that way. In this abstract, in this analysis, MET amplified non-small cell lung cancer patients were identified and offered tepotinib. So in this group, there are 24 patients who were treated on the VISION trial cohort B, and we observe a response rate of 42%. For a targeted therapy, having a 42% of response is really pretty encouraging. And the duration of response also is expected at multiple months. We showed that the therapy was particularly beneficial for patients who are treatment-naive. In that setting, the response rate can be as high as 70%. This time, this year, we updated our molecular analysis for this patient cohort trying to understand deeper, do we have other signals to help us to decide which patient could benefit more and which patient might benefit less and then need something else? In the molecular analysis, we find that focal MET amplification is quite important. In another word, if MET amplification is the only event, then more likely this MET TKI will work in that patient population. However, if the tumor also has p53 or RB loss or certain other genetic alterations, then the response rate can be more inferior. So I think we are starting to understand each of the molecular-driven patient population group into even more molecular detail, understanding the co-mutations’ impact to the clinical outcome. So I think this abstract is interesting in pointing directions of how to use an existing medication to patients to magnify the benefits that we can potentially achieve. So this year's North America Lung Conference was really productive. We had a lot of stimulating presentations and a lot of discussions. Other than the targeted therapy session, we have seen 2 exciting abstract on the immunotherapy updates. Other than that, we start to have more opportunities to learn about cancer screening, cancer prevention, smoking addiction, and then the cancer survivorship. There are 2 abstracts presented at the oral section for that topic as well. So this meeting is particularly interesting opportunity for North America investigators, especially in their junior stage, to network, to present their work, and then to have exposure to major investigators in the field as well. Dr. Le: Thank you, Dr. Le. 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. 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