Next Steps in the Management of EGFR Exon 20 Insertion–Positive mNSCLC


Closing out their discussion on mobocertinib data and the EXCLAIM cohort, experts share hope for the future management of the EGFR exon 20 insertion–positive mNSCLC.


Gregory Riely, MD, PhD: With regard to the next steps, I think we’ve spent a good amount of time talking about the sequence question because I think that is important. Where do you see we’re going for patients with EGFR exon 20 insertions?

Tarek Mekhail, MD: Well, it’s figuring out, No. 1, if there is a better drug than the other. Actually, I would rather have all the drugs, but knowing in which group would each work, because they have different mechanisms of action. We talked about MOBO [mobocertinib], we talked about amivantamab. There’s CLN-081. There are other drugs that might be coming down the pipeline. Maybe we’ll be lucky enough to figure out in whom every one of these classes work. If we do, maybe we’ll move it to the front line in some patients. Combinations are something that I think may happen. I know the attempt at mobocertinib in combination with chemotherapy was not easy to say the least. There are a lot of adverse effects. I really hope that we will get a drug ultimately that’s easier. This is my hope. Until then, we need to work with what we have.

Gregory Riely, MD, PhD: I think we’ve seen with the development of new ALK inhibitors, and we’ve seen with the development of EGFR inhibitors, that the first generation is not always the best. We have a drug that establishes that this is a group of patients who can benefit from this strategy, but with the second and third generations of these drugs, we can often significantly improve upon both the efficacy and the tolerance. I think if we can get more specific EGFR exon 20 insertion drugs, I think it’s likely that we’re going to be able to have a better therapeutic window, leading to better outcomes for our patients.

Tarek Mekhail, MD: Perhaps also with better CNS [central nervous system] activity, because in the study that we’re talking about, a lot of patients, particularly the patients who had brain metastasis at baseline, the brain was the first site of progression of disease in the majority of patients. I’m not optimistic that mobocertinib has good CNS activity, and I don’t believe amivantamab does either, so hopeful in the future we will have a strategy by which we control the brain disease.

Gregory Riely, MD, PhD: I completely agree. I think this has been a great conversation around this paper, where we saw the efficacy of mobocertinib, an EGFR exon 20 insertion–specific tyrosine kinase inhibitor for patients with EGFR exon 20 insertion–mutated non–small cell lung cancer. We saw reasonable efficacy data and tolerability that we can certainly manage as medical oncologists. It was a great conversation, and I’m happy to have this conversation with you.

Tarek Mekhail, MD: Thank you, Dr Riely. That was fun.

Transcript edited for clarity.

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