Hundreds of trials are being conducted to evaluate combination of newer targeted drugs as well as immunotherapy. Our aim was to compare efficacy and safety of combination versus single non-cytotoxic anticancer agents. We searched PubMed (01/01/2001 to 03/06/2018) (and, for immunotherapy, ASCO and ESMO abstracts (2016 through March 2018)) for randomized clinical trials that compared a single non-cytotoxic agent (targeted, hormonal, or immunotherapy) versus a combination with another non-cytotoxic partner. Efficacy and safety endpoints were evaluated in a meta-analysis using a linear mixed-effects model (guidelines per PRISMA Report).We included 95 randomized comparisons (single vs. combination non-cytotoxic therapies) (59.4%, phase II; 41.6%, phase III trials) (29,175 patients (solid tumors)). Combinations most frequently included a hormonal agent and a targeted small molecule (23%). Compared to single non-cytotoxic agents, adding another non-cytotoxic drug increased response rate (odds ratio [OR]=1.61, 95%CI 1.40-1.84)and prolonged progression-free survival (hazard ratio [HR]=0.75, 95%CI 0.69-0.81)and overall survival (HR=0.87, 95%CI 0.81-0.94) (all p<0.001), which was most pronounced for the association between immunotherapy combinations and longer survival. Combinations also significantlyincreased the risk of high-grade toxicities (OR=2.42, 95%CI 1.98-2.97) (most notably for immunotherapy and small molecule inhibitors) and mortality at least possibly therapy related (OR: 1.33, 95%CI 1.15-1.53) (both p<0.001) (absolute mortality = 0.90% (single agent) versus 1.31% (combinations)) compared to single agents. In conclusion, combinations of non-cytotoxic drugs versus monotherapy in randomized cancer clinical trials attenuated safety, but increased efficacy, with the balance tilting in favor of combination therapy, based on the prolongation in survival.

中文翻译：

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抗癌药物组合的功效和安全性：一项针对随机试验的荟萃分析，重点是免疫疗法和基因靶向化合物。

正在进行数百项试验，以评估新型靶向药物和免疫疗法的组合。我们的目的是比较联合用药与单一非细胞毒性抗癌药的疗效和安全性。我们在PubMed（2001年1月1日至2018年6月3日）（以及免疫治疗方面的ASCO和ESMO摘要（2016年至2018年3月））中搜索了比较单一非细胞毒性药物（靶向，激素，或免疫疗法）与另一种非细胞毒性伴侣的组合。使用线性混合效应模型（根据PRISMA报告的指南）在荟萃分析中评估疗效和安全性终点。我们纳入了95项随机比较（单项治疗与联合治疗的非细胞毒性治疗）（59.4％，第二阶段； 41.6％， III期临床试验）（29,175例患者（实体瘤））。最常见的组合包括激素药和靶向小分子（23％）。与单一非细胞毒性药物相比，添加另一种非细胞毒性药物可提高缓解率（几率[OR] = 1.61，95％CI 1.40-1.84），并延长无进展生存期（危险比[HR] = 0.75，95％ CI 0.69-0.81）和总生存期（HR = 0.87，95％CI 0.81-0.94）（均p <0.001），这在免疫疗法与更长生存期之间的关联中最为明显。组合还显着增加了高毒性的风险（OR = 2.42，95％CI 1.98-2.97）（最显着的是用于免疫治疗和小分子抑制剂）和至少与治疗有关的死亡率（OR：1.33，95％CI 1.15-1.53 ）（均为p <0.001）（绝对死亡率= 0.90％（单药）和1.31％（组合））。结论，