Dr. Bazhenova on Sequencing Beyond Progression in EGFR-Mutant NSCLC

Lyudmila A. Bazhenova, MD, medical oncologist, professor of clinical medicine, University of California, San Diego, discusses sequencing beyond progression on osimertinib (Tagrisso) in EGFR-mutant non—small cell lung cancer (NSCLC).

For patients with EGFR-mutant disease, physicians should treat with osimertinib until progression. Before deciding on a second-line therapy, the type of progression should be defined, be it systemic or localized. If the disease is localized, the patient is not losing weight or energy, and they’re not having new severe pain in more than 1 part of the body, patients can receive local therapy to the progressing lesion and continue osimertinib, explains Bazhenova.

If the patient has a systemic progression, indicated by rapid growth in more than 1 site, a post-progression biopsy is recommended. If the biopsy comes back with a C797S mutation, the patient may be amenable to first-generation EGFR TKIs—in which case, gefitinib (Iressa) or erlotinib (Tarceva) could be used. BRAF mutations may develop as a resistance mechanism to osimertinib. MET amplification has also been seen, and there are clinical trials for those patients, one of which is called SAVANNAH. In that trial, which is open at many institutions, patients are receiving a combination of osimertinib and savolitinib, says Bazhenova.