BRAF mutation predicts survival after immunotherapy across multiple cancer types.

Recently studies in selected tumors suggested that BRAF mutation may associates with survival benefit from immune checkpoint inhibitor (ICI) therapy. To broadly investigate this association at a pan-cancer level, we analyzed two independent ICI treatment cohorts (MSKCC: n = 1630, and Dana-Farber: n = 249). Patients with BRAF-mutant tumors exhibit better overall survival in the MSKCC cohort (Hazard ratio [HR] = 0.55, 95% confidence interval [CI]: 0.43-0.72; P < 0.001) and the result is validated by the Dana-Farber cohort (HR = 0.68, 95% CI: 0.46-0.99; P = 0.045). A multivariate analysis adjusting tumor mutational burden, mismatch repair status, cancer type, age and sex confirmed the results (adjusted HR = 0.58, 95% CI = 0.43-0.78; P < 0.001). Immunogenomic features analysis of TCGA dataset indicated that patients may respond to immunotherapy in various mechanisms. This finding substantially improves the therapeutic prospects for a sizeable fraction of patients who benefit from immunotherapy.