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

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.