Zhao Wangcheng, Yang Zhi, Fei Quanming, Hu Xinhang, Ouyang Yifan, Yi Xuyang, Xie Shouzhi, Wang Li, Huang Xingchun, He Yu, Luo Juan, Xiao Ye, Zhang Zhe, Yu Fenglei
Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.
Department of Thoracic and cardiovascular surgery and The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Int J Surg. 2025 Jul 1;111(7):4756-4771. doi: 10.1097/JS9.0000000000002480. Epub 2025 May 20.
The safety profile of immune checkpoint blockade (ICB) in the adjuvant setting has not been well characterized. This study aims to summarize the incidences of adverse events (AEs) in patients with solid tumors receiving ICB in adjuvant setting, and evaluate the effect of ICB addition on incidences of these adverse events.
We searched public databases and relevant international conference proceedings up to 20 September 2024, to identify eligible randomized controlled trials evaluating the ICB-based treatments in adjuvant setting for patients with solid tumors. The primary outcomes included treatment-related death, treatment-related adverse events (TrAEs), immune-related adverse events (IrAEs), serious AEs, and discontinuation due to AEs. The GRADE approach was used to evaluate the certainty of evidence for primary outcomes.
Thirty-eight trials with 25 852 participants were included. Single-arm meta-analysis showed that combination therapies had a higher incidence of grade 3-4 TrAEs than PD-1/PD-L1 monotherapy, while anti-CTLA-4-based therapies exhibited higher discontinuation rates (49.7% [39.4-60.0] for anti-CTLA-4 monotherapy) versus other ICB strategies. Treatment-related death was rare, occurring in 63 of 16 272 participants receiving adjuvant ICB-based treatments. The pairwise meta-analysis revealed that the addition of ICB was associated with increased treatment-related deaths (OR [95% CI]: 1.713 [1.117-2.628]), although this association was observed only in the CTLA-4 blockade and not in the PD-1 or PD-L1 blockade. ICB addition also increased incidences of TrAEs, IrAEs, serious AEs, and discontinuations, with consistent results across blockade types. Additionally, ICB addition was associated with higher incidences of 37 types of AEs, including 20 grade 3-4 events. Most results had moderate evidence quality.
Adding ICB in adjuvant setting was associated with increased AEs, but the toxicity profile was largely similar to that in the advanced setting.
辅助治疗中免疫检查点阻断（ICB）的安全性尚未得到充分描述。本研究旨在总结接受辅助治疗的实体瘤患者中不良事件（AE）的发生率，并评估添加ICB对这些不良事件发生率的影响。
我们检索了截至2024年9月20日的公共数据库和相关国际会议记录，以确定评估基于ICB的辅助治疗对实体瘤患者疗效的合格随机对照试验。主要结局包括治疗相关死亡、治疗相关不良事件（TrAE）、免疫相关不良事件（IrAE）、严重AE以及因AE导致的停药。采用GRADE方法评估主要结局证据的确定性。
纳入了38项试验，共25852名参与者。单臂荟萃分析表明，联合治疗的3-4级TrAE发生率高于PD-1/PD-L1单药治疗，而基于抗CTLA-4的治疗与其他ICB策略相比停药率更高（抗CTLA-4单药治疗为49.7%[39.4-60.0]）。治疗相关死亡罕见，在接受基于ICB的辅助治疗的16272名参与者中有63例发生。成对荟萃分析显示，添加ICB与治疗相关死亡增加相关（OR[95%CI]：1.713[1.117-2.628]），尽管这种关联仅在CTLA-4阻断中观察到，而在PD-1或PD-L1阻断中未观察到。添加ICB还增加了TrAE、IrAE、严重AE和停药的发生率，不同阻断类型的结果一致。此外，添加ICB与37种AE的发生率较高相关，包括20种3-4级事件。大多数结果的证据质量为中等。
在辅助治疗中添加ICB与AE增加相关，但毒性特征与晚期治疗基本相似。
