Patient Selection, Sequencing, and Co-Mutations in KRAS G12C-Mutant NSCLC

This segment focuses on individualized treatment approaches for KRAS G12C-mutant NSCLC. Faculty discuss the role of monotherapy versus combination strategies, emphasizing that response rate alone is insufficient and that durability of response, particularly with immunotherapy, remains a central consideration. The panel examines the influence of STK11 and KEAP1 co-mutations on treatment selection and immunotherapy responsiveness, and how these alterations already inform clinical decision-making. Discussion addresses sequencing questions raised by moving effective combinations into the first-line setting, resistance mechanisms including MET amplification, and the challenge that a substantial proportion of patients may not reach second-line therapy. Faculty also review early data on CTLA-4-based regimens in patients with STK11 and KEAP1 co-mutations.