NSCLC: Standard Treatment Approaches for EGFR Exon 20 Insertion Mutations


Current standard-of-care approaches toward the management of patients with non–small cell lung cancer with EGFR exon 20 insertion mutations.


Catherine Ann Shu, MD: In the past, prior to our new FDA approvals, I was giving my EGFR exon 20 insertion patients chemotherapy. That was typically carboplatin and pemetrexed. Sometimes I would add bevacizumab. I don’t use immunotherapy with them. They tend to be on the nonsmoker spectrum, so immunotherapy is less exciting for them. Also, you don’t want to use immunotherapy in these EGFR patients who may go on to a tyrosine kinase inhibitor because there can be some adverse effects seen with the 2, 1 after the other.

In general, I’ve been using chemotherapy. I’ve also had patients come to me from their oncologist who didn’t realize that this was a special type of EGFR mutation—they thought this was a typical EGFR mutation—and just started them on osimertinib. When they came to me, I explained that this was an EGFR exon 20 insertion, which is different from the traditional EGFR mutation. I probably wouldn’t start them on osimertinib. I’ve definitely switched some of those people to chemotherapy.

Nowadays, we’re lucky to have the new FDA approval of several agents for EGFR exon 20 insertion patients. If my patient progressed on platinum, I’m now putting them on amivantamab, which is the new Janssen EGFR-MET bispecific antibody. I’ve had very nice results with that drug. That’s where I am in the second line after platinum.

Erminia Massarelli, MD, MS, PhD: My standard treatment for patients with exon 20 insertion mutations in the first line—outside clinical trials, because at our institution [City of Hope] we do have many clinical trials—in non–small cell lung cancer has been with chemotherapy plus or minus immunotherapy. I also use the 4-drug approach, which is platinum, Taxol, osimertinib, and amivantamab. However, there are more and more data showing that exon 20 insertion mutations don’t respond well to immunotherapy. Even if a patient has a high PD-L1, I wouldn’t advise immunotherapy alone as first-line treatment. I would treat the patient with chemotherapy and then eventually add immunotherapy. That’s my first-line approach.

After progression of first line, we have many clinical trials. We participated in several that led to the approval of amivantamab and mobocertinib, and we have more ongoing trials.

Transcript edited for clarity.

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