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Combination therapy of BRAF inhibitors for advanced melanoma with BRAF V600 mutation: a systematic review and meta-analysis

Abstract Background: Although BRAF inhibitors have been used to treat advanced melanoma with BRAF mutation, combination strategies are suggested due to acquired resistance to BRAF inhibitors. Objective: To assess the efficacy of BRAF inhibitor-based combination therapy for the treatment of advanced melanoma with BRAF mutation. Methods: We conducted a systematic review and meta-analysis of studies that compared BRAF inhibitor-based combination therapy with BRAF inhibitor monotherapy. We searched MEDLINE, EMBASE, the Cochrane Library and relevant conference proceedings. The random-effects inverse variance and Mantel–Haenszel methods were used to pool the results. Results: Four randomized controlled trials and one cohort study were identified. A combination therapy with BRAF inhibitors and MEK inhibitors was used in all studies. The combined hazard ratios of overall survival (OS) and progression-free survival (PFS) comparing combination therapy with monotherapy were 0.70 [95% confidence interval (CI) 0.62–0.78] and 0.59 (95% CI 0.55–0.63), respectively. The combined risk ratio of objective response rate (ORR) was 1.30 (95% CI 1.20–1.40), which meant more patients achieved complete/partial responses in combination therapy group than those in the monotherapy group. Conclusions: Combination therapy with BRAF inhibitors and MEK inhibitors significantly improved OS, PFS, and ORR in patients with advanced melanoma with BRAF mutation.