Dr. Shum on Mechanisms of Resistance in Oncogene-Driven NSCLC

Elaine Shum, MD, medical oncologist, NYU Langone’s Perlmutter Cancer Center, discusses mechanisms of resistance in patients with oncogene-driven non—small cell lung cancer (NSCLC).

Based on data from the phase III FLAURA and ALEX studies, osimertinib (Tagrisso) and alectinib (Alecensa) have become the recommended frontline treatments for patients with EGFR-mutant and ALK-positive NSCLC, respectively. Physicians are still learning why tumors develop mechanisms of resistance, says Shum. Although there is no substantial insight into why this occurs, there is reason to believe that these targeted agents isolate a clone and allow for another clone to drive the disease undetected. Future studies involving more biopsies at the time of progression will hopefully shed more light on this issue, she adds.

For patients who have developed resistance to treatment, combination therapy with various TKIs may be a potential strategy, says Shum, although toxicity may become an issue. Additionally, some anecdotal studies have shown improved outcomes with an EGFR inhibitor and MET inhibitor in EGFR-mutant patients with MET amplification.