Network meta-analysis of therapies for previously untreated advanced BRAF-mutated melanoma

Abstract

Background: The spectrum of treatment options for patients with metastatic BRAF-mutated melanoma is broad, spanning multiple treatment classes. However, there is a lack of head-to-head evidence comparing targeted and immunotherapies. The purpose of this study is to conduct a network meta-analysis (NMA) in previously untreated, BRAF-mutated melanoma patients and estimate the relative efficacy of systemic therapies for this patient population at the treatment level.

Methods: The literature review included searches of MEDLINE, EMBASE, and the Cochrane Central Registry of Controlled Trials (CENTRAL) to November 2018. Randomized controlled trials of previously untreated patients with advanced melanoma were eligible if at least one intervention was either a targeted or immune therapy. Relative treatment effects were estimated by fixed effect Bayesian NMAs on progression-free survival (PFS) and overall survival (OS), based on the hazard ratio.

Results: Combination dabrafenib with trametinib (HR 0.22 [95% CrI 0.17, 0.28] vs dacarbazine) and combination vemurafenib with cobimetinib (HR 0.22 [95% CrI 0.17, 0.29] vs dacarbazine) were likely to rank as the most favorable treatment options for PFS, while combination nivolumab with ipilimumab was likely to be the most efficacious in terms of OS (HR 0.33 [0.24, 0.47] vs dacarbazine).

Conclusions and relevance: The findings highlight the efficacy of combination PD-1 with CTLA-4 inhibitors and combination BRAF with MEK inhibitors in the treatment of advanced melanoma. However, as few trials informed each treatment comparison, research is needed to further refine our understanding of this complex and rapidly evolving treatment landscape.

Keywords: BRAF-mutated melanoma; Immunotherapy; Network meta-analysis; Targeted therapy.