Novel Therapy for NSCLC With EGFR Exon 20 Insertion Mutation


Panelists review the data behind treatment options for non–small cell lung cancer expressing EGFR exon 20 insertion mutation.


Benjamin Levy, MD: Let’s move on to EGFR exon 20, a less common mutation than EGFR exon 19 and 21, and undruggable 10 years ago, but we have new drugs that have come around and made an impact. Chaitali, do you want to walk us through some of the data we have with amivantamab and mobocertinib and some of the data we saw yesterday from CLN-081 presented by Helena Yu, [MD]?

Chaitali Nangia, MD: I think this is interesting, as you said until now it’s been considered undruggable, but these new data are really exciting. The new drug, amivantamab from the CHRYSALIS [trial], had a good response rate in this tough population who have had multiple lines of therapy, a good progression-free survival [PFS], and the toxicity in my opinion was pretty decent too. Then mobocertinib, they’re almost similar, the third aspect compares the two to see if one is more toxic and what’s the efficacy. They are really similar in response rates and progression-free survival. I think the differences would be the patient population. Amivantamab had a more Asian patient population not prior treated with immunotherapy, whereas the one with mobocertinib did have prior PD-1–exposed patients. I think those factors play in. One is oral, one is IV [intravenous], so some patients prefer one to the other. I think that’s how I look at it, but 2 new drugs, similar efficacy, similar toxicity profiles, and not too high on toxicity, but different patient characteristics in the studies.

Benjamin Levy, MD: I think we saw the data yesterday, we don’t have it here, but the CLN-081 drug, and correct me if I’m wrong, in the exon 20 group, highly pretreated or pretreated with prior therapies, a response rate in the 30% to 35% range, and we’ll have to see how this all works out. It’s a reasonably well-tolerated drug, perhaps better than mobocertinib.

Chaitali Nangia, MD: Or amivantamab.

Jonathan Wesley Riess, MD: The duration of response was notable, although small numbers, so that’ll be interesting to see follow-up. I look at these as the first-generation drugs, analogous toerlotinib and osimertinib. The response rate and PFS are good, but they’re not like osimertinib and the FLAURA trial, and so hopefully newer agents will come along. I generally do mobocertinib first mainly because it’s oral and it’s hard to distinguish a meaningful difference with the cross-trial comparisons. But I would just highlight that these EGFR exon 20 insertions are so heterogeneous in terms of their location on EGFR exon 20, and the number of amino acid substitutions. I think what’s going to happen in the future is you’re going to have a heat map with all these different EGFR exon 20 drugs, and some insertions may be more amenable to one EGFR exon 20drug vs another, and we’ll plug in or look up what the insertion is, and it’ll spit out what drug works the best.

Benjamin Levy, MD: I went into lung cancer because it was easy. It’s gotten really complicated as we’re subdividing out the EGFR exon 20s. It’s not easy anymore. It’s a win for the patient, and us but it’s gotten very nuanced and very complicated.

Heather Wakelee, MD: I liked Alex’s comment earlier, “I just look it up.”I think we all need to be open about that, you can’t assume you know. It’s important that you look [things up].

Transcript edited for clarity.

Related Videos
Pasi A. Jänne, MD, PhD, discusses an exploratory analysis from the FLAURA2 trial of osimertinib plus chemotherapy in treatment-naive, EGFR-mutant NSCLC.
Saad J. Kenderian, MB, CHB
Jaime Schneider, MD, PhD
Benjamin Creelan, MD
Neel P. Chudgar, MD
Paul K. Paik, MD, clinical director, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center
Joshua K. Sabari, MD, assistant professor, Department of Medicine, New York University Grossman School of Medicine
Raj Singh, MD
Arya Amini, MD