EGFR Exon 20 Insertion as a Therapeutic Target in Non-small Cell Lung Cancer - Episode 8

Clinical Pearls: EGFR Exon 20 Insertion+ NSCLC Treatment

Joel Neal, MD, PhD, and Alexander I Spira, MD, PhD, FACP, provide an overview of their major conclusions and clinical pearls for the treatment approach of EGFR Exon 20 Insertion+ NSCLC.

Joel Neal, MD, PhD:Let’s take a minute and review everything we discussed and talked about—our major conclusions. One of my first major conclusions would be EGFR exon 20 insertions are a mutation that’s targetable. It’s really 1 of these new can’t-miss mutations in the treatment of non–small cell lung cancer. First and foremost, testing is important, and testing by next-generation sequencing—by blood if it’s negative and by tissue until you find a molecular driver as key.

Dr Spira, do you have pearls about what to do if you’re stuck in that situation where you say, “I’ve been waiting 3 or 4 weeks for mutational testing. This patient might have an EGFR mutation.” What’s your treatment approach? That’s 1 of the pearls that we didn’t go over, but 1 I always like to stress to our community colleagues.

Alexander I. Spira, MD, PhD, FACP: A couple of things. No. 1 is to test. Those of us who are knee-deep in the treatment of lung cancer are always used to testing. I was part of a group when we published some of the community-based data, and only 50% of patients had 5 biomarkers to check, not even getting to 7, 8, 9, or 10—whatever number we’re at this week; I can’t even keep track of it. So test, please. You can’t put somebody on a targeted therapy if you don’t test for that targeted therapy. I know that seems obvious, but it’s something we need to talk to people about.

It’s about education. I always try to educate people. You probably can wait. There are very few patients who can’t wait those 2 weeks to come back. In an ideal world, I always like to wait. But if you really can’t wait—there’s always that subset of patients who are in the hospital—I usually start them on carboplatin-pemetrexed for adenocarcinoma, and carboplatin-Taxol for non. I often lead out the immunotherapy, because obviously, there’s an increased concern of toxicity, and you’re not going to go wrong with 1 cycle of chemotherapy while you’re waiting for this to come back. For me, those are 2 pearls I like to do. Testing is key, and certainly, that approach, for me, has worked very well. There’s only 1 patient over the last year for whom I couldn’t wait for the markers to come back. Most people want to wait for that mutation. There were some patients who were inpatient. They get treated there, but those are few and far between.

Joel Neal, MD, PhD: My personal strategies are to provide reassurance and maybe do another scan. If you can show them after a month that the tumor hasn’t grown that much, then they can wait 2 or 3 more weeks to do it. I’d rather do a new CT scan than start treatment prematurely. Avoiding immunotherapy is 1 of my pearls as well. We don’t have as much data about how these new EGFR exon 20 inhibitors get along after immunotherapy. Presumably, some of the patients in these studies did have immunotherapy before.

With some drugs, the risk of pneumonitis is significantly higher, so avoiding immunotherapy until we excluded all the mutation drivers is important. That would be my recommendation and preference too. What about when we find somebody and say, “We have a hit,” and they’re newly diagnosed? How do we factor in the new approvals of these EGFR exon 20 inhibitors or think about clinical trials? What do you do, and what would you recommend to community colleagues who are too far to drive away from where you are?

Alexander I. Spira, MD, PhD, FACP: For me, it is all about clinical trials. Those are the first thing on NCCN [National Comprehensive Cancer Network] Guidelines, and everybody forgets that. It’s OK to send out for a clinical study. We saw a ton of patients referred—as did you, as did all of us—on mobocertinib. Most of them really benefited; that’s my first-and-foremost guideline. I’m still following the label. Outside of a trial, amivantamab and—with the presumed approval—mobocertinib, when it gets approved, will be in the second-line setting. For me, it’s chemotherapy first, followed by 1 of those drugs in the second line, based on the data that we have so far. How about you?

Joel Neal, MD, PhD: In the first-line setting, I’d probably still go with chemotherapy, with or without bevacizumab, as we talked about initially. In the second-line setting, the new FDA approvals are compelling. There’s amivantamab, and probably others will be expected shortly.

Alex, I really want to thank you for chatting with me about this subject that’s so close to both of us. Over the last few years, it has been incredibly exciting. We’ve gone from an untargetable target that—which was so frustrating to find, a situation where we’d say, “There aren’t any good treatments other than chemotherapy and standard-of-care treatments for non–small cell lung cancer”—to having a number that have shown activity in this setting, as well as new FDA approvals and probably more to come.

It’s really a fantastic story in science and translational medicine from bench to bedside. I want to thank everybody out there who listened as well as all the patients and their families who helped with participation in the clinical trials that helped these drugs advance. I also put in a brief plug that there are groups for all of these patients out there. There’s the exon 20 group, which focuses on and provides patient advocates for those patients and family members, and everybody else who has EGFR and also HER2 [human epidermal growth factor receptor 2] exon 20–mutant tumors. That’s a good resource online for anybody who’s looking. Thank you very much. Alex, do you have any final words?

Alexander I. Spira, MD, PhD, FACP: No, Joel, you said it very well. Thanks, everybody. I just want to echo Joel and give my thanks to all the clinical trial participants. It has been an amazing scientific run, and it’s only going to get more exciting over time.

This transcript has been edited for clarity.