Therapeutic efficacy and safety of combined BRAF and MEK inhibition in patients with malignant melanoma: a meta-analysis

OncoTargets and Therapy

关键词: Efficacy;    Safety;    Melanoma;    Meta-analysis;    BRAF inhibition;    MEK inhibition;   

DOI  :  

来源: DOAJ

【 摘 要 】

Peng Chen,1,* Fuchao Chen,2,* Benhong Zhou1,31Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, Hubei, 2Department of Pharmacy, Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei, 3School of Pharmaceutical Sciences, Wuhan University, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workBackground: Recent clinical studies have shown that initial therapy with combined BRAF and mitogen-activated extracellular signal-regulated kinase (MEK) inhibition is more effective in metastatic melanoma than single-agent BRAF inhibitors. However, the response rates with single-agent BRAF are low. Thus, the objective of this study was to conduct a meta-analysis of randomized controlled trials to compare the efficacy and adverse events risk between monotherapy and combination therapy.Materials and methods: Searches were made in PubMed and EMBASE electronic databases and conference abstracts published by the American Society of Clinical Oncology from 2000 to 2017. Outcomes included overall response, progression-free survival, and overall survival, as well as the incidence rate of adverse events.Results: Eight trials comprising 2,664 patients were included in the meta-analysis. Patients with combined therapies showed superior results compared to those with BRAF inhibitors alone for the following: overall response rate (combined relative risk [RR] =1.34, 95% confidence interval [95% CI]: 1.24–1.45, P<0.00001), progression-free survival (combined hazards ratio [HR] =0.58, 95% CI: 0.52–0.64, P<0.00001), and overall survival rate (combined HR =0.70, 95% CI: 0.62–0.80, P<0.00001). Patients with combination therapies had higher incidence of adverse events including pyrexia (combined RR =2.00, 95% CI: 1.40–2.84), nausea (combined RR =1.41, 95% CI: 1.03–1.94), diarrhea (combined RR =1.50, 95% CI: 1.08–2.06), and vomiting (combined RR =1.87, 95% CI: 01.52–2.31) compared to those with BRAF inhibitors alone.Conclusion: These data suggested that the combined BRAF and MEK inhibition was associated with a significant improvement in overall response, progression-free survival, and overall survival, but increased the incidence of adverse events among the patients with BRAF V600-mutated metastatic melanoma. Further large-scale, high-quality, placebo-controlled, double-blind trials are needed to confirm this conclusion.Keywords: efficacy, safety, melanoma, meta-analysis, BRAF inhibition, MEK inhibition

【 授权许可】

Unknown