Dr. Oxnard on Detecting Resistance Mechanisms After Treatment With Osimertinib

Geoffrey R. Oxnard, MD, physician, assistant professor of medicine, Harvard Medical School, Dana-Farber Cancer Institute, discusses resistance mechanisms that occur in patients with EGFR-positive T790M non—small cell lung cancer (NSCLC) following treatment with osimertinib (Tagrisso).

Oxnard and colleagues are currently investigating the question of, "what happens after patients develop resistance to osimertinib? What is the next treatment approach?" In patients undergoing a biopsy for resistance to osimertinib, practitioners look for 2 types of resistance, Oxnard explains. For example, there are patients who develop resistance later on treatment with osimertinib, maintain T790M on resistance, and acquire new EGFR mutations such as C797S.

However, in patients who experience early resistance to osimertinib, T790M is suppressed and other competing mechanisms overgrow T790M, such as small cell transformation and MET amplification. These are poor prognosis factors, and researchers must identify targeted therapies to target these newer mechanisms of resistance. For example, the TATTON trial is investigating osimertinib combined with a MET inhibitor to suppress these competing clones, he adds.