Background The introduction of antibodies targeting programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) into clinical practice has had a revolutionary effect on cancer treatment. However, the incidence and risk of fatal adverse events (FAEs) following PD-1/PD-L1 inhibitor administration are controversial. Methods We performed a systematic search for randomized controlled trials (RCTs) of PD-1/PD-L1 inhibitors (atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab) in Embase, PubMed, the Cochrane database, and abstracts presented at American Society of Clinical Oncology and European Society of Medical Oncology from inception to July 2018. FAEs were extracted from each study and pooled to calculate overall incidence and odds ratios (ORs). Results In total, 20 RCTs involving 12,398 patients with solid tumors were included in this study. The overall incidence of FAEs with PD-1/PD-L1 inhibitors was 0.43% [95% confidence interval (CI), 0.25-0.66%]. However, the incidences of FAEs varied significantly by tumor type and median follow-up time. Compared with conventional agents, the application of PD-1/PD-L1 inhibitors significantly reduced the risk of FAEs (OR, 0.56; 95% CI, 0.35-0.89; p = 0.015). Moreover, trial sequential analysis confirmed that our results were solid and reliable; further studies were unlikely to alter this conclusion. FAEs occurred dispersed in major organ systems, with the most common mortalities appearing in the respiratory system (46.2%). Conclusions Compared with conventional treatment, PD-1/PD-L1 blockade monotherapy is associated with a significantly reduced risk of mortality in patients with solid tumors.

中文翻译：

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与程序性细胞死亡蛋白 1 或程序性细胞死亡配体 1 单药治疗癌症相关的致命不良事件。

背景 将靶向程序性细胞死亡蛋白 1 (PD-1) 和程序性细胞死亡配体 1 (PD-L1) 的抗体引入临床实践对癌症治疗产生了革命性的影响。然而，PD-1/PD-L1 抑制剂给药后致命不良事件 (FAE) 的发生率和风险存在争议。方法 我们在 Embase、PubMed、Cochrane 数据库和美国医学会发表的摘要中对 PD-1/PD-L1 抑制剂（atezolizumab、avelumab、durvalumab、nivolumab 和 pembrolizumab）进行了系统检索。临床肿瘤学和欧洲医学肿瘤学会从成立到 2018 年 7 月。从每项研究中提取 FAE，并汇总以计算总体发病率和优势比 (OR)。结果 总共有 20 项 RCT，涉及 12 项，本研究纳入了 398 例实体瘤患者。使用 PD-1/PD-L1 抑制剂的 FAE 总发生率为 0.43% [95% 置信区间 (CI)，0.25-0.66%]。然而，FAE 的发生率因肿瘤类型和中位随访时间而有显着差异。与传统药物相比，PD-1/PD-L1 抑制剂的应用显着降低了 FAE 的风险（OR，0.56；95% CI，0.35-0.89；p = 0.015）。此外，试验序贯分析证实我们的结果是可靠的；进一步的研究不太可能改变这一结论。FAEs分散在主要器官系统中，最常见的死亡发生在呼吸系统（46.2%）。结论 与常规治疗相比，