COMBINATION THERAPY OF BRAF INHIBITORS FOR ADVANCED MELANOMA WITH V600 BRAF MUTATION- A SYSTEMATIC REVIEW AND META-ANALYSIS

Author(s)

Kim S, Kim HT, Suh HS
Pusan National University, Busan, South Korea

OBJECTIVES: BRAF inhibitors were approved by US Food and Drug Administration as the treatment of patients with unresectable or metastatic melanoma with the BRAF V600E mutation, opening the era of targeted therapy. As acquired resistance to the BRAF inhibitors became problematic, however, combination strategies were suggested. We conducted a systematic review and meta-analysis to assess the efficacy of combination therapy including BRAF inhibitors as treatment of advanced melanoma with V600 BRAF mutation. METHODS: We searched MEDLINE, EMBASE and The Cochrane Library for randomized controlled trials (RCT), controlled clinical trials (CCT), cohort studies, and case-control studies. The primary outcomes were overall survival (OS) and progression-free survival (PFS) measured in hazard ratio (HR) or median. Secondary outcome was objective response rate (ORR). Using random effects model, we conducted meta-analyses to pool all results. RESULTS: We identify 5 eligible studies; 4 RCTs and 1 cohort. All five studies used combinations of BRAF inhibitors and MEK inhibitors. Data of 1872 participants were included in meta-analysis. The combined HR of OS was 0.70 (95% CI 0.62 to 0.78) and combined HR of PFS was 0.59 (95% CI 0.55 to 0.63), favoring the combination therapy. In all studies, median overall survival and median progression-free survival were longer in the combination therapy groups. The combined risk ratio of ORR was 1.30 (95% CI 1.20 to 1.40), which means more patients in combination therapy group achieved complete or partial responses than those in monotherapy group. CONCLUSIONS: Combination therapy of BRAF inhibitors and MEK inhibitors significantly improved overall survival, progression-free survival, and objective response rate in advanced melanoma with V600 BRAF mutation.

Conference/Value in Health Info

2016-05, ISPOR 2016, Washington DC, USA

Value in Health, Vol. 19, No. 3 (May 2016)

Code

PCN20

Topic

Clinical Outcomes

Topic Subcategory

Comparative Effectiveness or Efficacy

Disease

Oncology

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