Co-Mutation Status Association with Clinical Outcomes in Patients with -Mutant Non-Small Cell Lung Cancer.

co-mutations have shown association with poor prognosis in various solid tumors. For -mutated advanced non-small cell lung cancer (aNSCLC), conflicting results exist regarding its impact on survival. Clinical outcomes and genomic data were obtained retrospectively from the real-world (rw) de-identified clinicogenomic database. Patients who initiated therapy for -mutated aNSCLC between January 2014 and December 2020 were identified. Clinical outcomes were evaluated by -mutational status. In 356 eligible -mutated aNSCLC patients (median age 68 years), 210 (59.0%) had co-mutation and 146 (41.0%) had wild-type tumor. Unadjusted analysis showed significantly shorter survival in patients with co-mutation versus wild-type (rw progression-free survival [rwPFS]: HR = 1.4, 95% CI 1.1-1.9, = 0.0196; overall survival [OS]: HR = 1.6, 95% CI 1.1-2.2, = 0.0088). Multivariable analysis confirmed independent association between co-mutation and worse rwPFS (HR = 1.4, 95% CI 1.0-0.9, = 0.0280) and OS (HR = 1.4, 95% CI 1.0-2.0, = 0.0345). Directionally consistent findings were observed for response rates, and subgroups by -activating mutation and first-line (1 L) therapy, with more pronounced negative effect in 1 L -TKI subgroup. co-mutations negatively affected survival in patients with -mutated aNSCLC receiving standard 1 L therapy in real-world practice.