Rare Drivers in Metastatic Non-Small-Cell Lung Cancer with a Focus on EGFR Exon 20 Insertion Mutations - Episode 11

New Therapies for NSCLC With EGFR Exon 20 Insertions

Mark A. Socinski, MD, highlights the targeted agents available to treat non–small cell lung cancer with EGFR mutations.

Mark A. Socinski, MD: As I mentioned initially, this group of patients—the exon 20 insertion population—remains an unmet need. We have the recent approval of amivantamab in the second-line setting, and we expect more approvals to be coming along for drugs like mobocertinib, or perhaps poziotinib. Other drugs are under development. It’s still a little early to know how we’ll incorporate them into clinical practice. We do understand that there’s heterogeneity in exon 20 insertion mutations, so I don’t think we should assume that 1 size fits all here. We have a lot to learn. There are subsets of patients that, for instance, are more suitable for a drug like mobocertinib vs poziotinib or others and vice versa. I don’t think we know that yet, but that would be 1 of the questions.

I’ve mentioned amivantamab, which was recently FDA-approved in this setting. This is a bispecific antibody that has activity in the second-line setting and certainly is an option there. How do the TKIs [tyrosine kinase inhibitors] work? Should they be used before an antibody, or after an antibody? All these issues need to be sorted out. They are nice issues to have, because we have a number of drugs that are coming with activity that will aid us in sorting out the appropriate patient for which drug and the appropriate sequence of things ahead of us. I don’t think we have any specific guidelines with regard to how to do this.

The bottom line is this is a target that oncologists should be testing for. They should recognize that this is different from other EGFR mutations where FDA-approved TKIs are quite active. This is a separate group of patients with different challenges that require a different strategy with regard to other agents, as we’ve discussed in this brief interaction. It will be a helpful addition to the therapeutic armamentarium, as we’ve said.