Second-Line Sotorasib and Adagrasib Sequencing

Rajwanth R. Veluswamy, MD, MSCR, and Chinmay Jani, MD, of the Perlmutter Cancer Center at NYU Langone Health and the University of Miami Sylvester Comprehensive Cancer Center, discuss second-line sequencing with sotorasib and adagrasib in KRAS G12C-mutated non-small cell lung cancer. Both agents hold accelerated approval, sotorasib since May 2021 and adagrasib since December 2022, based on phase 1 and 2 data followed by randomized phase 3 trials against docetaxel; Dr. Veluswamy notes the progression-free survival benefit was marginal, about 5 to 6 weeks, and that most RAS-mutant non-small cell lung cancer is not G12C, leaving no targeted treatment currently available for those patients. He characterizes sotorasib and adagrasib as an important step forward primarily because of tolerability rather than efficacy: docetaxel is difficult to tolerate, while these oral agents are much better tolerated and avoid intravenous infusion, a distinction he considers clinically meaningful even given the modest survival gain.