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

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Pages 314-321 | Received 02 Mar 2017, Accepted 01 May 2017, Published online: 31 May 2017
 

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.

Acknowledgements

This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT & Future Planning(NRF-2016R1C1B1009198).

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT & Future Planning(NRF-2016R1C1B1009198).

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