Dr. Socinski on Mechanisms of Resistance in Lung Cancer

Mark A. Socinski, MD, executive medical director, AdventHealth Medical Group, discusses mechanisms of resistance in patients with lung cancer.

The biggest unmet need in lung cancer is understanding resistance mechanisms, Socinski says. There are drugs that can be highly effective for a limited period of time, so the question is, why doesn’t that activity last? There is something that happens in the tumor that turns a drug that was once beneficial into an agent that is no longer effective, and this is something that research needs to address.

In patients with EGFR-positive non—small cell lung cancer, EGFR TKIs are prolonging survival by several months—and even years in some cases—but patients are still developing progressive disease at some point. A major breakthrough was made in the field when T790M was discovered as a significant resistance mechanism to first- and second-generation TKIs. This discovery led to the development of osimertinib (Tagrisso), a third-generation EGFR TKI that is now being used in the frontline setting. Although this drug is more effective than the first- and second-generation EGFR TKIs, patients are still developing resistance to it. To date, investigators still do not understand what is driving this resistance.