Precision Medicine: Key Updates for Treatment of NSCLC - Episode 6

Treating Non–Small Cell Lung Cancer With an EGFR Exon 20 Insertion

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Benjamin Levy, MD: That is a great overview, Lyuda. Thank you for mentioning TAK-788 because it wasn’t presented at ASCO [American Society of Clinical Oncology Annual Meeting]. It had response rates of 40% to 45% and a median PFS [progression-free survival] of around 7 to 8 months. Outside these drugs, which are not ready for prime time in a clinic, how do you treat patients currently who are EGFR exon 20 mutated?

Lyudmila Bazhenova, MD: If I don’t have access to the study and no site within driving distance has access to the study, it is platinum doublet chemotherapy.

Benjamin Levy, MD: Becca, what are your thoughts on these drugs and where they’re heading? In general, what do you do for patients with EGFR exon 20 mutation? I’ll put you on the spot. When you’re using chemotherapy for these patients, do you use immunotherapy? Do you use bevacizumab? Do you just do chemotherapy?

Rebecca Heist, MD: Those are great questions. It is heartening to see some movement in exon 20, because for a long time it was just, “We have an EGFR mutation,” and then, “It’s exon 20.” It was really hard not to be able to offer good options to these patients. Having some drugs like JNJ-6372 and TAK-788 that have some nice signals of activity is very heartening.

I use chemotherapy as much as possible. I try to put patients on clinical trials. For that reason, I tend to avoid immunotherapy. In general, the immunotherapies have shown less activity in never smokers with driver mutations. There is a concern about increased toxicity, especially if you’re doing I/O [immuno-oncology] followed by a TKI [tyrosine kinase inhibitor], because of the long half-life of the I/O and concomitant toxicities. To avoid that, with the thought that perhaps they would be going on a study of a TKI, I tend to reserve I/O until very late in the course to be able to avoid toxicity issues like that.

Benjamin Levy, MD: Josh, I know you are the senior author for the JNJ-6372 drug, at least at the time of presentation at ASCO a couple of years ago. Do you have any thoughts on your experience, No. 1, with this drug, and No. 2, how you treat patients off-trial?

Joshua Bauml, MD: I’ve been impressed with the efficacy of the drug, as well as the relative tolerability of it. That first-day infusion reaction is a dramatic episode, so the first dose is administered over 2 days. Patients have it, and then it goes away. It’s been relatively safe. With the multiple drugs that exist, we have to consider the pros and cons of each, right? Amivantamab is a gigantic, bispecific monoclonal antibody, so it’s not going to have CNS [central nervous system] penetration. That is a limitation of that drug.

In contrast, if you look at the toxicity profile of TAK-788 and poziotinib, it’s significant. We saw the data with poziotinib presented at ASCO, but even TAK-788 has substantial amounts of mucositis. It has diarrhea. These are real limitations from these drugs. But there, you’re more likely to get CNS penetrance. It’s a balance issue.

My approach has been to generally use chemotherapy. Sometimes, I will incorporate immunotherapy. There’s some retrospective data indicating that patients with an exon 20 insertion are more likely than others with an EGFR mutation to respond to immunotherapy. In addition, because I’m less concerned about the cross-reactivity of immunotherapy with amivantamab, and that’s the trial that I have at my institution, I’m more likely to use immunotherapy in that setting.

Benjamin Levy, MD: It’s an interesting space. Time will tell how these drugs all shake out. I have used osimertinib at 160 mg off-trial. I haven’t been encouraged by the results. We saw some reasonable response rates and tolerability. There are certainly other drugs like JNJ-6372 and mobocertinib that may take the lead in treating these patients. I would say, off a trial, I generally fall into the camp of chemotherapy with bevacizumab, based on very little data. That’s generally why I offer it, but I can’t dispute immunotherapy and chemotherapy also being used for these patients.

Transcript Edited for Clarity