Overview of Available Therapies for EGFR Mutations in Lung Cancer


Mark A. Socinski, MD, discusses types of EGFR mutations in non–small cell lung cancer and the treatments that target these mutations.

Mark A. Socinski, MD, a medical oncologist and executive director (thoracic cancer) at the AdventHealth Cancer Institute, discusses types of EGFR mutations in non–small cell lung cancer (NSCLC) and the treatments that target these mutations.

According to Socinski, EGFR mutations are some of the most common alterations present in tumors, and researchers are still investigating the heterogeneity of different EGFR mutations. The most common are sensitivity mutations that are associated with response to targeted treatment, such as EGFR exon 19 deletions and EGFR exon 21 L858R mutations. Several tyrosine kinase inhibitors (TKIs) are approved by the FDA for these mutations, with osimertinib (Tagrisso) being the standard of care. Afatinib (Gilotrif) is approved to treat patients with other EGFR sensitivity mutations, including S768I, L861Q, and G719X.

Additionally, he notes that between 8% and 10% of EGFR mutations are EGFR exon 20 insertion mutations, which do not respond to osimertinib and other agents that target exon 19 or 21 alterations. Two targeted therapies, amivantamab (Rybrevant) and mobocertinib (Exkivity) are approved for this target, but only in the second line after patients have received platinum-based chemotherapy. Socinski says that these mutations represent an unmet need in the NSCLC setting.


0:08 | EGFR mutations are probably one of the more common genomic alterations that we see.... We're still kind of in evolution in terms of thinking about the heterogeneity of even EGFR mutations. Most of the EGFR mutations are what we refer to as the common mutations or sensitivity mutations. These are EGFR exon 19 deletions, as well as the exon 21 L858R mutation. We have 5 TKIs that are approved in this space; however, the standard of care is osimertinib. That is my first-line choice with either the exon 19 or the exon 21s. We do have a small group of atypical EGFR sensitivity mutations where afatinib is indicated.

Then separate from the sensitivity...mutations are the next most common group, about 8% to 10% of all EGFR mutations, which are the exon 20 insertion mutations. Now these are not sensitive to the currently available TKIs that are FDA approved. We do have amivantamab and mobocertinib that are approved following platinum-based chemotherapy. So there are options there, but certainly this is a space that I would say is relatively unmet need and we need more options in this particular subset of the EGFR mutations.

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