Divarasib as Compared with Sotorasib or Adagrasib in KRAS G12C-Mutated NSCLC.

Divarasib improved progression-free survival in previously treated KRAS G12C-mutated advanced or metastatic NSCLC, reaching 9.8 months versus 5.7 months with control (HR 0.58).

• Why it matters: First-generation KRAS G12C inhibitors leave room for better outcomes in this setting, and a more potent, selective option needed confirmation in a randomized phase 3 trial.
• What they did: In a phase 3, international, open-label study, patients were randomized to divarasib 400 mg once daily (n=167) or control (n=171; 156 sotorasib, 15 adagrasib), with progression-free survival assessed by blinded independent central review.
• The result: Divarasib also increased overall survival (17.7 vs 12.0 months; HR 0.56) and confirmed response (58.4% vs 32.3%), with fewer grade 3–4 treatment-related adverse events (24.6% vs 34.5%).