Treatment- and immune-related adverse events of immune checkpoint inhibitors in advanced lung cancer.
Treatment- and immune-related adverse events of immune checkpoint inhibitors in advanced lung cancer.
复制标题
免疫检查点抑制剂治疗晚期肺癌的治疗和免疫相关不良事件
DOI：
10.1042/bsr20192347
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发表时间：
2020-05-29
影响因子：
4
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Shao J;Wang C;Ren P;Jiang Y;Tian P;Li W
背景：免疫检查点抑制剂（ICIs）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不良事件和免疫相关不良事件对临床实践具有重要意义。
材料与方法：系统检索PubMed、Embase、Cochrane图书馆以及主要会议论文集，查找所有使用PD - 1/PD - L1/CTLA - 4抑制剂治疗肺癌的随机对照试验（RCTs）。结果包括治疗相关不良事件（TRAEs）以及几种器官特异性免疫相关不良事件（IRAEs）。
结果：纳入24项随机对照试验，涉及14256名患者。免疫检查点抑制剂治疗在任何级别治疗相关不良事件的发生率方面存在显著差异（风险比：0.90；95%置信区间：0.84 - 0.95；P = 0.001），且3 - 5级治疗相关不良事件的发生频率更低（风险比：0.65；95%置信区间：0.51 - 0.82；P < 0.001）。在非小细胞肺癌（NSCLC）中接受免疫检查点抑制剂治疗的患者报告的治疗相关不良事件比小细胞肺癌（SCLC）患者少。抗PD - 1抑制剂相比抗PD - L1抗体和抗CTLA - 4药物，治疗相关不良事件的风险更低。最常见的器官特异性免疫相关不良事件是甲状腺功能减退，发生率为8.7%。肺炎和肝炎的发生率分别达到4.5%和4.0%。与对照组患者相比，接受免疫检查点抑制剂药物治疗的患者发生每种器官特异性不良事件（包括结肠炎、肝炎、肺炎、甲状腺功能减退和垂体炎）的风险更高。
结论：免疫检查点抑制剂治疗比化疗更安全，尤其是在非小细胞肺癌中使用抗PD - 1抗体等免疫检查点抑制剂单药治疗。与标准治疗相比，免疫检查点抑制剂药物增加了器官特异性免疫相关不良事件的风险，尽管总体发生率仍然较低。
Background: 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. Materials and methods: 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). Results: 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. Conclusions: 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.