Sabari Reviews KRAS G12C Inhibitors in NSCLC

Joshua K. Sabari, MD, assistant professor, Department of Medicine at NYU Grossman School of Medicine, and director of High Reliability Organization Initiatives at the Perlmutter Cancer Center, discusses the importance of targeting the KRAS biomarker and what inhibitors currently exist for patients with KRAS G12C-mutant advanced solid tumors.

Currently, there are 2 approved KRAS G12C inhibitors, adagrasib (Krazai) and sotorasib (Lumakras), for patients with advanced non–small cell lung cancer (NSCLC). According to Sabari, while there are data to support the use of these agents, response rates remain lower than what has been seen in the EGFR space.

Sabari highlights the need for more combination strategies and options to provide better outcomes for these patients.

Transcription:

0:10 | KRAS G12C is quite common. It makes up about 13%-14% of all non–small cell lung cancers. When you take a step back and look at KRAS in general, it makes up about 30% of non–small cell lung cancer. KRAS G12C was debated whether it was actionable or not for many years. Sotorasib was the first drug to show activity in the setting in the phase 2 study, with about a 37% response rate. Adagrasib came a little bit later. Both [are] now FDA-approved and showed a 43% response rate. Both agents had progression-free survival in that 6 to 6 and a half month range with overall survival in that 12 or 13 month range. I think clearly, we've established that KRAS G12C is clearly a driver alteration and one that is actionable.

1:00 | Now, if you compare this to the EGFR space where we see responses of 80%, PFS of 18-20 months, and overall survival of 38 or 39 months, we are nowhere near where we are in the EGFR space with KRAS at the moment. So clearly, we need to do better and we need to think about either combination strategies or how to move these agents to the frontline setting to better benefit our patients.