Dr. Patil on the Development of KRAS G12C Inhibitors in Lung Cancer

Pradnya D. Patil, MD, FACP, Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, discusses the development of KRAS G12C inhibitors in lung cancer.

KRAS mutations were identified in lung cancer decades ago; however, developing a targeted therapy against the RAS pathway has been difficult, Patil explains. Significant research led to the development of the KRAS G12C inhibitors sotorasib (Lumakras) and adagrasib (MRTX849). Sotorasib was approved by the FDA on May 28, 2021, for use as first-line treatment of patients with non–small cell lung cancer whose tumors harbor KRAS G12C mutations and who have received at least 1 prior systemic therapy.

Unlike TKIs, KRAS G12C inhibitors are allele specific, which could account for the numerically modest response rates demonstrated by the agents, Patil says. However, these agents offer a novel class of drugs to this specific patient population that has historically been very challenging to treat, Patil concludes.