Efficacy and safety of BRAF inhibition alone versus combined BRAF and MEK inhibition in melanoma: a meta-analysis of randomized controlled trials

Mengdong Liu, Xuekang Yang, Jiaqi Liu, Bin Zhao, Weixia Cai, Yan Li and Dahai Hu _

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Oncotarget. 2017; 8:32258-32269. https://doi.org/10.18632/oncotarget.15632

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Mengdong Liu1,*, Xuekang Yang1,*, Jiaqi Liu1, Bin Zhao1, Weixia Cai1, Yan Li1 and Dahai Hu1

1Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China

*These authors have contributed equally to this work

Correspondence to:

Dahai Hu, email: [email protected]

Keywords: efficacy, adverse events, BRAF inhibition, MEK inhibition, melanoma

Received: July 22, 2016     Accepted: November 14, 2016     Published: February 23, 2017


Recent clinical studies have shown that combination therapy of BRAF and MEK inhibition provides more survival benefit than BRAF inhibition monotherapy. However, the adverse events due to BRAF and MEK inhibitors impact the physical comfort and social life of patients. Thus, in this study we have undertaken a meta-analysis of randomized controlled trials to compare the efficacy and adverse events risk between monotherapy and combination therapy. We identified the relevant studies by searching PubMed, EMBASE and Google scholar databases, between the year January 2000 and May 2016. Based on the heterogeneity, the fixed- or random-effects models were employed to analyze the efficacy and the incidence rate of adverse events. In addition, the subgroup analyses were conducted to overcome the effects of heterogeneity. Finally, our study included five RCTs, involving 1730 patients for this meta-analysis. The fixed-effects model demonstrated that combination therapy of BRAF and MEK inhibition provided more survival benefit in terms of ORR, PFS and OS (P < 0.00001). But, the combination therapy also significantly increased the incidences of pyrexia, chills, vomiting, chorioretinopathy, retinal detachment, hypertension, night sweats, increased aspartate aminotransferase and creatine kinase levels (P < 0.05) as compared to monotherapy. But, based on the significantly better survival outcomes, the combined BRAF and MEK inhibition will obviously be the mainstay therapy for the BRAF V600-mutant melanoma. However, a set of adverse events should be paid attention when physicians consider combination therapy.

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