Chul Kim, MD, MPH, an attending physician at MedStar Health and an assistant professor of medicine at Georgetown University, discusses overcoming mechanisms of resistance to TKIs in non–small cell lung cancer (NSCLC).
Chul Kim, MD, MPH, an attending physician at MedStar Health and an assistant professor of medicine at Georgetown University, discusses overcoming mechanisms of resistance to TKIs in non—small cell lung cancer (NSCLC).
Investigators are exploring several strategies to overcome resistance mechanisms to TKIs in the lung cancer space. Specifically, in EGFR-mutant NSCLC, combination strategies have shown success, says Kim. For example, data from the phase III NEJ009 trial demonstrated a significant improvement in overall survival with the combination of gefitinib (Iressa), carboplatin, and pemetrexed versus gefitinib alone in patients with EGFR-activating mutations. Osimertinib (Tagrisso), a third-generation EGFR TKI, may show similar promise when used in combination with pemetrexed and osimertinib, but those studies are ongoing, adds Kim.
The second strategy under exploration involves isolating the mechanism of resistance in each patient and intervening with the appropriate targeted agent. For example, in a presentation from the 19th World Conference on Lung Cancer, investigators identified RET fusions in patients who had been treated with second-line osimertinib. These patients were treated with osimertinib and a RET inhibitor. The combination achieved partial responses, which were ongoing at 4 months, says Kim.