Chen Peng, Chen Fuchao, Zhou Benhong
Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, Hubei.
Department of Pharmacy, Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei.
Onco Targets Ther. 2017 Nov 13;10:5391-5403. doi: 10.2147/OTT.S147438. eCollection 2017.
Recent clinical studies have shown that initial therapy with combined and mitogen-activated extracellular signal-regulated kinase (MEK) inhibition is more effective in metastatic melanoma than single-agent inhibitors. However, the response rates with single-agent 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 mono-therapy and combination therapy.
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.
Eight trials comprising 2,664 patients were included in the meta-analysis. Patients with combined therapies showed superior results compared to those with inhibitors alone for the following: overall response rate (combined relative risk [RR] =1.34, 95% confidence interval [95% CI]: 1.24-1.45, <0.00001), progression-free survival (combined hazards ratio [HR] =0.58, 95% CI: 0.52-0.64, <0.00001), and overall survival rate (combined HR =0.70, 95% CI: 0.62-0.80, <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 inhibitors alone.
These data suggested that the combined 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 V600-mutated metastatic melanoma. Further large-scale, high-quality, placebo-controlled, double-blind trials are needed to confirm this conclusion.
近期临床研究表明，对于转移性黑色素瘤，联合使用[药物名称未明确，推测为 BRAF 抑制剂之类]和丝裂原活化细胞外信号调节激酶（MEK）抑制剂进行初始治疗比单药[药物名称未明确，推测为 BRAF 抑制剂之类]抑制剂更有效。然而，单药[药物名称未明确，推测为 BRAF 抑制剂之类]的缓解率较低。因此，本研究的目的是对随机对照试验进行荟萃分析，以比较单药治疗和联合治疗之间的疗效及不良事件风险。
检索了 PubMed 和 EMBASE 电子数据库以及美国临床肿瘤学会 2000 年至 2017 年发表的会议摘要。结局指标包括总缓解率、无进展生存期、总生存期以及不良事件发生率。
荟萃分析纳入了八项试验，共 2664 例患者。与单独使用[药物名称未明确，推测为 BRAF 抑制剂之类]抑制剂的患者相比，联合治疗的患者在以下方面显示出更好的结果：总缓解率（联合相对危险度[RR]=1.34，95%置信区间[95%CI]：1.24 - 1.45，P<0.00001）、无进展生存期（联合风险比[HR]=0.58，95%CI：0.52 - 0.64，P<0.00001）和总生存率（联合 HR =0.70，95%CI：0.62 - 0.80，P<0.00001）。与单独使用[药物名称未明确，推测为 BRAF 抑制剂之类]抑制剂的患者相比，联合治疗的患者不良事件发生率更高，包括发热（联合 RR =2.00，95%CI：1.40 - 2.84）、恶心（联合 RR =1.41，95%CI：1.03 - 1.94）、腹泻（联合 RR =1.50，95%CI：1.08 - 2.06）和呕吐（联合 RR =1.87，95%CI：01.52 - 2.31）。
这些数据表明，联合使用[药物名称未明确，推测为 BRAF 抑制剂之类]和 MEK 抑制剂可显著改善总缓解率、无进展生存期和总生存期，但会增加 V600 突变的转移性黑色素瘤患者的不良事件发生率。需要进一步开展大规模、高质量、安慰剂对照、双盲试验来证实这一结论。
