Dr. Goldberg on Resistance to Osimertinib for NSCLC

Sarah B. Goldberg, MD, MPH, an assistant professor of medicine at the Yale School of Medicine and Yale Cancer Center, discusses resistance to first- or second-line osimertinib (Tagrisso) for patients with EGFR-positive non—small cell lung cancer (NSCLC).

After second-line osimertinib, patients have already received a first- or second-generation EGFR inhibitor. Patients who develop resistance to osimertinib in this setting have been known to have a T790M mutation in addition to an acquired resistance to the drug, says Goldberg. For example, there are patients who develop the C797S mutation in addition to T790M.

However, this is different when patients develop resistance to osimertinib in the first-line setting, explains Goldberg. When osimertinib is used in the first-line setting, the T790M mutation does not develop. Instead, physicians can see different mechanisms of resistance, such as C797S. MET amplification can also play a role in both settings, but physicians are unsure of whether it is more common in the first-line or second-line setting. Additionally, small cell transformation is seen after second-line osimertinib, but data are unclear regarding its prevalence in the first-line setting.