癌症患者免疫检查点抑制剂治疗相关免疫不良反应的荟萃分析。

Meta-analysis of immune-related adverse events of immune checkpoint inhibitor therapy in cancer patients.

机构信息

Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.

Central Research Laboratory,Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.

出版信息

Thorac Cancer. 2020 Sep;11(9):2406-2430. doi: 10.1111/1759-7714.13541. Epub 2020 Jul 8.

BACKGROUND

Immune checkpoint inhibitors (ICIs) have significant clinical efficacy in the treatment of non-small cell lung cancer (NSCLC); however, the incidence of immune-related adverse events (irAEs) of up to 50% has prevented their widespread use. With the increase in the use of ICIs alone or as combination therapy, clinicians are required to have a better understanding of irAEs and be able to manage them systematically. In this study, we aimed to assess the incidence of irAEs associated with ICIs.

METHODS

We searched PubMed, Embase, and the Web of Science databases, and also included relevant literature references to widen our search. The relevant data with inclusion criteria were performed using RevMan 3.6.0 for meta-analysis. We undertook a systematic literature search which included published data up to December 2019.

RESULTS

Overall, 147 articles and 23 761 cancer patients with 11 different ICI treatment-related (grade 1-5 and 3-5) irAEs were included in the study. There were 46 articles on pembrolizumab (6598 patients), 27 on nivolumab (3576 patients), 13 on atezolizumab (2787 patients), 12 on avelumab (3213 patients), 10 on durvalumab (1780 patients), 22 on ipilimumab (4067 patients), eight on tremelimumab (1158 patients), three on JS001 (223 patients), four on camrelizumab (SHR-1210) (178 patients), one on sintilimab (96 patients), and one on cemiplimab (85 patients). Grade 1-5 irAEs were: cytotoxic T lymphocyte antigen 4 (CTLA-4) (82.87%), programmed cell death 1 (PD-1) (71.89%), and programmed cell death ligand-1 (PD-L1) (58.95%). Subgroup analysis was: Avelumab (44.53%), durvalumab (66.63%), pembrolizumab (67.25%), atezolizumab (68.77%), nivolumab (76.25%), Ipilimumab (82.18%), and tremelimumab (86.78%). Grade 3-5 irAEs were: CTLA-4 (27.22%), PD-1(17.29%), and PD-L1(17.29%). Subgroup analysis was: Avelumab (5.86%), durvalumab (13.43%), atezolizumab (14.45%), nivolumab (15.72%), pembrolizumab (16.58%), tremelimumab (22.04%), and ipilimumab (28.27%).

CONCLUSIONS

This meta-analysis confirmed that anti-PD-1 and anti-PD-L1 inhibitors had a lower incidence of irAEs compared with anti-CTLA-4 inhibitors.

背景

免疫检查点抑制剂（ICIs）在治疗非小细胞肺癌（NSCLC）方面具有显著的临床疗效；然而，高达 50%的免疫相关不良事件（irAEs）的发生率阻碍了它们的广泛应用。随着单独使用或联合治疗的 ICIs 的使用增加，临床医生需要更好地了解 irAEs，并能够系统地管理它们。在这项研究中，我们旨在评估与 ICIs 相关的 irAEs 的发生率。

方法

我们搜索了 PubMed、Embase 和 Web of Science 数据库，并纳入了相关文献的参考文献以扩大搜索范围。使用 RevMan 3.6.0 对符合纳入标准的相关数据进行荟萃分析。我们进行了系统的文献搜索，包括截至 2019 年 12 月的已发表数据。

结果

总体而言，研究纳入了 147 篇文章和 23761 例接受 11 种不同的 ICI 治疗相关（1-5 级和 3-5 级）irAEs 的癌症患者。其中，46 篇文章关于 pembrolizumab（6598 例患者），27 篇关于 nivolumab（3576 例患者），13 篇关于 atezolizumab（2787 例患者），12 篇关于 avelumab（3213 例患者），10 篇关于 durvalumab（1780 例患者），22 篇关于 ipilimumab（4067 例患者），8 篇关于 tremelimumab（1158 例患者），3 篇关于 JS001（223 例患者），4 篇关于 camrelizumab（SHR-1210）（178 例患者），1 篇关于 sintilimab（96 例患者），1 篇关于 cemiplimab（85 例患者）。1-5 级 irAEs 为：细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）（82.87%）、程序性细胞死亡蛋白 1（PD-1）（71.89%）和程序性死亡配体 1（PD-L1）（58.95%）。亚组分析为：avelumab（44.53%）、durvalumab（66.63%）、pembrolizumab（67.25%）、atezolizumab（68.77%）、nivolumab（76.25%）、ipilimumab（82.18%）和 tremelimumab（86.78%）。3-5 级 irAEs 为：CTLA-4（27.22%）、PD-1（17.29%）和 PD-L1（17.29%）。亚组分析为：avelumab（5.86%）、durvalumab（13.43%）、atezolizumab（14.45%）、nivolumab（15.72%）、pembrolizumab（16.58%）、tremelimumab（22.04%）和 ipilimumab（28.27%）。