First-line advanced melanoma treatments: PD-1 + CTLA-4 inhibitors offer best PFS/OS but higher toxicity; PD-1 monotherapy provides favorable efficacy-safety balance. BRAF/MEK inhibitors suit BRAF-mutant patients needing rapid response, though immunotherapy yields better long-term outcomes. Personalized therapy is recommended based on mutation status, disease burden, and toxicity tolerance. This evidence concerns the gene BRAF and melanoma.