Liu Tingting, Jin Bo, Chen Jun, Wang Hui, Lin Shuiyu, Dang Jun, Li Guang
Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China Department of Radiation Oncology, Anshan Cancer Hospital, Anshan, China.
Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.
Ther Adv Med Oncol. 2020 Jul 15;12:1758835920940927. doi: 10.1177/1758835920940927. eCollection 2020.
This network meta-analysis assessed the comparative risk of grade 3-5 and grade 5 treatment-related adverse events (TRAEs) for immune checkpoint inhibitors (ICIs), either alone or in combination with other modalities, for cancer treatment.
PubMed, Embase, Cochrane Library, Web of Science, and recent predominant oncology congresses were searched for relevant phase II and phase III randomized controlled trials (RCTs). As outcomes, grade 3-5, and grade 5 TRAE outcomes were reported as odds ratios and 95% confidence intervals.
In 67 RCTs involving 36,422 patients and 19 ICIs, the incidence of grade 3-5 and grade 5 TRAEs was 17.9% and 0.8% with ICI monotherapy and 46.3% and 1.4%, respectively, with combinatorial therapy. Pneumonitis was the most common cause of grade 5 TRAEs following either monotherapy (16.3%) or combinatorial therapy (11.4%). Regarding grade 3-5 TRAEs, atezolizumab + chemotherapy (CT) and antiangiogenic therapy (AT) (atezolizumab + CAT), pembrolizumab + CT, ipilimumab + CT, and atezolizumab + CT were more toxic than any ICI monotherapy, pembrolizumab or nivolumab + radiotherapy (RT), and ICIs dual therapy (durvalumab + tremelimumab and nivolumab + ipilimumab). Tremelimumab, ipilimumab, durvalumab, and pembrolizumab were, however, associated with higher grade 5 TRAEs than combinatorial treatments. Atezolizumab + CAT was the most toxic and nivolumab + RT was the least toxic of combinatorial treatments; among monotherapies, tremelimumab and avelumab were the most and least toxic, respectively. The toxicity ranking changed with type of grade 3-5 TRAEs.
Compared with combinatorial therapy, ICI monotherapy caused lower grade 3-5 TRAEs, but some monotherapies resulted in a higher incidence of fatal TRAEs. Atezolizumab + CAT and nivolumab + RT were the most and least toxic of combinatorial treatments, respectively, and tremelimumab and avelumab were the most and least toxic of the monotherapies, respectively.
本网络荟萃分析评估了免疫检查点抑制剂（ICI）单独或与其他治疗方式联合用于癌症治疗时，3 - 5级及5级治疗相关不良事件（TRAEs）的比较风险。
检索PubMed、Embase、Cochrane图书馆、Web of Science以及近期主要的肿瘤学大会，查找相关的II期和III期随机对照试验（RCT）。作为研究结果，3 - 5级和5级TRAE结果以比值比和95%置信区间的形式报告。
在涉及36422例患者和19种ICI的67项RCT中，ICI单药治疗的3 - 5级和5级TRAEs发生率分别为17.9%和0.8%，联合治疗分别为46.3%和1.4%。肺炎是单药治疗（16.3%）和联合治疗（11.4%）后5级TRAEs的最常见原因。关于3 - 5级TRAEs，阿替利珠单抗 + 化疗（CT）和抗血管生成治疗（AT）（阿替利珠单抗 + CAT）、帕博利珠单抗 + CT、伊匹木单抗 + CT以及阿替利珠单抗 + CT比任何ICI单药治疗、帕博利珠单抗或纳武利尤单抗 + 放疗（RT）以及ICI双联治疗（度伐利尤单抗 + 曲美木单抗和纳武利尤单抗 + 伊匹木单抗）毒性更大。然而曲美木单抗、伊匹木单抗、度伐利尤单抗和帕博利珠单抗与联合治疗相比，5级TRAEs发生率更高。阿替利珠单抗 + CAT是联合治疗中毒性最大的，纳武利尤单抗 + RT是联合治疗中毒性最小的；在单药治疗中，曲美木单抗毒性最大，阿维鲁单抗毒性最小。毒性排名随3 - 5级TRAEs的类型而变化。
与联合治疗相比，ICI单药治疗导致的3 - 5级TRAEs较低，但一些单药治疗导致致命TRAEs的发生率较高。阿替利珠单抗 + CAT和纳武利尤单抗 + RT分别是联合治疗中毒性最大和最小的，曲美木单抗和阿维鲁单抗分别是单药治疗中毒性最大和最小的。
