• Immunotherapy · May 2019

    Comparative Study

    Comparative efficacy of combination immunotherapy and targeted therapy in the treatment of BRAF-mutant advanced melanoma: a matching-adjusted indirect comparison.

    • Michael B Atkins, Ahmad Tarhini, Michael Rael, Komal Gupte-Singh, Elliott O'Brien, Corey Ritchings, Sumati Rao, and David F McDermott.
    • Georgetown Lombardi Comprehensive Cancer Center, Washington, DC 20057, USA.
    • Immunotherapy. 2019 May 1; 11 (7): 617-629.

    AimComparison of clinical outcomes of nivolumab + ipilimumab versus BRAF + MEK inhibitors (dabrafenib + trametinib or vemurafenib + cobimetinib) in BRAF-mutant advanced melanoma.MethodsMatching-adjusted indirect comparisons were conducted between nivolumab + ipilimumab (CheckMate 067/069 studies) and BRAF + MEK inhibitors (COMBI-d, COMBI-v and coBRIM studies). Overall survival (OS), progression-free survival and objective response rates were assessed.ResultsAfter adjusting, nivolumab + ipilimumab showed improved OS versus dabrafenib + trametinib (hazard ratio [HR] = 0.64; 95% CI: 0.46-0.89) or vemurafenib + cobimetinib (HR = 0.56; 95% CI: 0.36-0.89); OS outcomes were similar at 1 year, with benefits emerging after 12 months; progression-free survival and objective response rates were similar. Grade 3/4 adverse events occurred in 54.1% with nivolumab + ipilimumab, 31.6% with dabrafenib + trametinib and 59.5% with vemurafenib + cobimetinib.ConclusionNivolumab + ipilimumab had significantly improved clinical outcomes versus BRAF + MEK inhibitors, with benefits increasing after longer follow-up. Ongoing randomized trials directly comparing these treatments are necessary to prospectively validate these findings.

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