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Approved first-line treatments for patients with BRAF V600-mutant advanced melanoma include nivolumab (a programmed cell death protein 1 inhibitor) plus ipilimumab (a cytotoxic T lymphocyte antigen-4 inhibitor; NIVO+IPI) and the BRAF/MEK inhibitors dabrafenib plus trametinib (DAB+TRAM), encorafenib plus binimetinib (ENCO+BINI), and vemurafenib plus cobimetinib (VEM+COBI). Results from prospective randomized clinical trials (RCTs) comparing these treatments have not yet been reported. This analysis evaluated the relative efficacy and safety of NIVO+IPI versus DAB+TRAM, ENCO+BINI, and VEM+COBI in patients with BRAF-mutant advanced melanoma using a matching-adjusted indirect comparison (MAIC). ⋯ Results of this MAIC demonstrated durable OS and PFS benefits for patients with BRAF-mutant advanced melanoma treated with NIVO+IPI compared with BRAF/MEK inhibitors, with the greatest benefits noted after 12 months.