Talking KRAS-Targeted Therapy in NSCLC With Dr. Riess

Welcome to a very special edition of OncLive^® On Air! I’m your host today, Caroline Seymour.

OncLive^® On Air is a podcast from OncLive, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In today’s episode, sponsored by Amgen, we had the pleasure of speaking with Jonathan W. Riess, MD, MS, associate professor of medicine in the Division of Hematology and Oncology at the University of California Davis Comprehensive Cancer Center, to discuss KRAS-targeted treatment strategies in advanced non–small cell lung cancer (NSCLC).

KRAS mutations are the most common oncogenic driver in NSCLC, representing approximately 25% of all lung adenocarcinoma cases, said Riess. Despite being the first driver to be discovered in NSCLC, drug development has lagged behind other more recently discovered alterations. This is due, in part, to the belief that mutations in KRAS locked the gene in its guanosine triphosphate (GTP)–bound state which trigger downstream pathway activations when in fact, KRAS mutations impair the binding of GTPase-activating proteins that can catalyze the conversion back to its inactive guanosine diphosphate (GDP)–bound state.

Direct KRAS G12C inhibitors, however, can return GTP-bound KRAS to its inactive GDP-bound state, said Riess; this has translated into improved response rates and preliminary signs of durability in patients with previously treated KRAS G12C–mutant NSCLC.

In our exclusive interview, Riess discussed the excitement surrounding KRAS G12C inhibitors in NSCLC, preliminary efficacy and safety data with AMG 510, and additional research regarding co-mutations and combinations that could lead to further refinement of the potential role of the agent in the landscape.