Comparing Sotorasib and Adagrasib Tolerability

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, compare the tolerability of sotorasib and adagrasib in KRAS G12C-mutated non-small cell lung cancer. Dr. Veluswamy reports more gastrointestinal toxicity, including diarrhea, nausea, and vomiting, with adagrasib, and more hepatotoxicity with sotorasib, a distinction that matters most for patients who recently received immunotherapy. He notes that the KRYSTAL-1 central nervous system cohort for adagrasib included patients with untreated brain metastases and showed similar intracranial and systemic efficacy, whereas the sotorasib trial included only stable or previously treated brain metastases, a factor Dr. Jani weighs with central nervous system involvement. Because neither drug has shown an overall survival benefit or converted to full approval, both faculty favor shared decision-making: explaining the available progression-free survival data, favoring these oral, better-tolerated agents over chemotherapy, and offering a clinical trial first when available.