Department of Respiratory and Critical Care Medicine, West China Medical School/West China Hospital, Sichuan University, Chengdu, China.
Department of Clinical Research Center for Respiratory Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Biosci Rep. 2020 May 29;40(5). doi: 10.1042/BSR20192347.
Immune checkpoint inhibitors (ICIs) emerged as the preferred therapy in advanced lung cancer, understanding the treatment- and immune-related adverse events of these drugs is of great significance for clinical practice.
PubMed, Embase, Cochrane library and major conference proceedings were systematically searched for all randomized controlled trials (RCTs) in lung cancer using PD-1/PD-L1/CTLA-4 inhibitors. The outcomes included treatment-related adverse events (TRAEs) and several organ specific immune-related adverse events (IRAEs).
24 RCTs involving 14,256 patients were included. There was a significant difference for ICI therapy in the incidence of any grade of TRAEs (RR: 0.90; 95%CI: 0.84-0.95; P=0.001) and a lower frequency of grade 3-5 of TRAEs (RR: 0.65; 95%CI: 0.51-0.82; P<0.001). Patients treated with ICI therapy in non-small-cell lung cancer (NSCLC) were less reported TRAEs than in small cell lung cancer (SCLC). A lower risk of TRAEs was favored by anti-PD-1 inhibitors over anti-PD-L1 antibodies and anti-CTLA-4 drugs. The most common organ specific IRAE was hypothyroidism that occurred 8.7%. The incidence of pneumonitis and hepatitis reached 4.5% and 4.0% respectively. Compared with patients treated in control arms, those treated with ICI drugs were at higher risk for each organ specific adverse event including colitis, hepatitis, pneumonitis, hypothyroidism and hypophysitis.
ICI therapy was safer than chemotherapy, especially ICI monotherapy such as anti-PD-1 antibodies in NSCLC. Compared with standard treatments, ICI drugs increased the risk of organ-specific IRAEs, although the overall incidence remained low.
免疫检查点抑制剂（ICI）已成为晚期肺癌的首选治疗方法，了解这些药物的治疗相关和免疫相关不良事件对临床实践具有重要意义。
系统检索了 PubMed、Embase、Cochrane 图书馆和主要会议论文集，以获取使用 PD-1/PD-L1/CTLA-4 抑制剂治疗肺癌的所有随机对照试验（RCT）。结果包括治疗相关不良事件（TRAEs）和几种特定器官的免疫相关不良事件（IRAEs）。
纳入了 24 项涉及 14256 名患者的 RCT。ICI 治疗在任何等级 TRAEs 的发生率（RR：0.90；95%CI：0.84-0.95；P=0.001）和 3-5 级 TRAEs 的发生率（RR：0.65；95%CI：0.51-0.82；P<0.001）方面存在显著差异。ICI 治疗在非小细胞肺癌（NSCLC）患者中的 TRAEs 发生率低于小细胞肺癌（SCLC）患者。与抗 PD-L1 抗体和抗 CTLA-4 药物相比，抗 PD-1 抑制剂更有利于降低 TRAEs 的风险。最常见的特定器官 IRAE 是甲状腺功能减退症，发生率为 8.7%。肺炎和肝炎的发生率分别达到 4.5%和 4.0%。与接受对照组治疗的患者相比，接受 ICI 药物治疗的患者发生每种特定器官不良事件的风险更高，包括结肠炎、肝炎、肺炎、甲状腺功能减退症和垂体炎。
ICI 治疗比化疗更安全，特别是在 NSCLC 中，ICI 单药治疗如抗 PD-1 抗体。与标准治疗相比，ICI 药物增加了特定器官 IRAEs 的风险，尽管总体发生率仍然较低。
