Understanding EGFR Resistance in Patients With MET-Amplified NSCLC

Lecia V. Sequist, MD, MPH, director, Center for Innovation in Early Cancer Detection, Massachusetts General Hospital, and Landra Family associate professor of medicine, Harvard Medical School, says that oncologists have developed a better understanding of what causes resistance to EGFR inhibitors in patients with non—small cell lung cancer (NSCLC) through preclinical studies and biopsies.METamplification was found to be one of the major causes of resistance to newer generation EGFR-targeted drugs.

Oncologists are getting ahead of these amplifications by testing combination regimens that include an EGFR inhibitor and a MET inhibitor. As single agents, these drugs are not sufficient for patients, but the combination therapies allow physicians to attack the resistance pathway, says Sequist. This theory was tested in one of the arms of the phase Ib TATTON trial in previously treated patients withEGFR-mutant NSCLC (NCT02143466).

The study combined EGFR inhibitor osimertinib (Tagrisso) with MET inhibitor savolitinib, despite other preclinical trials in NSCLC that did not show positive results with combining these 2 types of inhibitors. What makes the TATTON trial different is that it’s being done in a biomarker-selected population and it’s the first clinical trial to do so. Good overall response rates and duration of response were seen in both cohorts of the study, and the combination was considered tolerable.