Zhao Bin, Zhao Hong, Zhao Jiaxin
Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, 109 Xueyuan West Rd, Wenzhou, 325035, China.
The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Ther Adv Med Oncol. 2020 Feb 6;12:1758835919895753. doi: 10.1177/1758835919895753. eCollection 2020.
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.
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).
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; = 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%).
Compared with conventional treatment, PD-1/PD-L1 blockade monotherapy is associated with a significantly reduced risk of mortality in patients with solid tumors.
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。
我们在Embase、PubMed、Cochrane数据库以及美国临床肿瘤学会和欧洲医学肿瘤学会从创刊至2018年7月发表的摘要中，对PD-1/PD-L1抑制剂（阿特珠单抗、阿维鲁单抗、度伐鲁单抗、纳武单抗和帕博利珠单抗）的随机对照试验（RCT）进行了系统检索。从每项研究中提取FAE，并进行汇总以计算总体发生率和比值比（OR）。
本研究共纳入20项涉及12398例实体瘤患者的RCT。PD-1/PD-L1抑制剂导致的FAE总体发生率为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异。与传统药物相比，PD-1/PD-L1抑制剂的应用显著降低了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。FAE分散发生在主要器官系统中，最常见的死亡出现在呼吸系统（46.2%）。
与传统治疗相比，PD-1/PD-L1阻断单药治疗可显著降低实体瘤患者的死亡风险。
