Osimertinib, Chemotherapy, EGFR Mutations, and Advanced NSCLC

In a phase 3 randomized trial (JAMA, n=294), adding chemotherapy to first-line osimertinib in advanced EGFR-mutated non-small cell lung cancer with concurrent TP53 mutations extended investigator-assessed median progression-free survival from 15.6 to 34.0 months (HR 0.44; 95% CI 0.32-0.60). TP53 co-mutation is a known marker of inferior outcomes on EGFR-TKI monotherapy, and this is the first randomized trial to test intensified first-line therapy in that subgroup. Overall survival data remain immature (30.6% maturity), so the survival benefit is not yet established; grade 3 or higher adverse events were more frequent with the combination.