免疫检查点抑制剂的癌症类型特异性不良事件：一项系统评价和荟萃分析。

Cancer type-specific adverse events of immune checkpoint inhibitors: A systematic review and meta-analysis.

作者信息

Tong Xuhui, Tang Rong, Xu Jin, Wang Wei, Du Qiong, Shi Si, Yu Xianjun

机构信息

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

Heliyon. 2025 Jan 2;11(1):e41597. doi: 10.1016/j.heliyon.2024.e41597. eCollection 2025 Jan 15.

DOI:10.1016/j.heliyon.2024.e41597

PMID:39866435

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11757769/

Abstract

BACKGROUND

The distribution of adverse events (AEs) triggered by immune checkpoint inhibitors (ICIs) across different cancer types has never been demonstrated.

METHODS

Randomised controlled trials exclusively assessing ICI monotherapy in cohorts of over 100 patients were considered. Our primary outcome was a comprehensive summary of the distribution of all-grade treatment-related adverse events (TRAEs) as well as serious TRAEs (CTCAE grade 3 or higher) across different malignancies. The study is registered with PROSPERO CRD42023387934.

FINDINGS

75 trials that enrolled over 100 patients were included. While investigating the incidence of each TRAE across various cancers, we found special linkages existed between certain TRAEs and particular cancer types. In anti-PD-1 monotherapy group, melanoma patients experienced the most frequent fatigue (31.1 %, 95 % CI 29.7%-32.5 %); the incidences of severe pneumonitis and other respiratory disorders were highest in Hodgkin lymphoma (4.1 %, 95 % CI 1.5%-8.6 %; 4.1 %, 95 % CI 1.5%-8.6 %, respectively). Among individuals undergoing single-agent anti-PD-L1, higher frequency of all-grade pruritus occurred in 19.0 % of renal cell carcinoma (RCC) patients (95 % CI 15.2%-23.2 %), and the highest probability of developing other severe musculoskeletal disorders was observed in patients with RCC (6.2 %, 95 % CI 4.0%-9.0 %). In anti-CTLA-4 monotherapy, the incidences of both all-grade and severe diarrhea occurred most frequently in prostate cancer patients (41.9 %, 95 % CI 37.9%-47.9; 14.8 %, 95 % CI 11.5%-18.7 %, respectively).

INTERPRETATION

This is the first comprehensive study addressing the distribution of various TRAEs across cancer types. Our research emphasizes the significance of considering cancer-specific TRAEs when using ICIs for treatment.

摘要

背景

免疫检查点抑制剂（ICI）引发的不良事件（AE）在不同癌症类型中的分布情况从未得到证实。

方法

纳入仅评估100例以上患者队列中ICI单药治疗的随机对照试验。我们的主要结局是全面总结不同恶性肿瘤中所有级别的治疗相关不良事件（TRAE）以及严重TRAE（CTCAE 3级或更高）的分布情况。该研究已在PROSPERO注册，注册号为CRD42023387934。

研究结果

纳入了75项纳入100例以上患者的试验。在调查各种癌症中每种TRAE的发生率时，我们发现某些TRAE与特定癌症类型之间存在特殊联系。在抗PD-1单药治疗组中，黑色素瘤患者疲劳发生率最高（31.1%，95%CI 29.7%-32.5%）；霍奇金淋巴瘤患者严重肺炎和其他呼吸系统疾病的发生率最高（分别为4.1%，95%CI 1.5%-8.6%；4.1%，95%CI 1.5%-8.6%）。在接受单药抗PD-L1治疗的个体中，19.0%的肾细胞癌（RCC）患者出现全级别瘙痒的频率更高（95%CI 15.2%-23.2%），RCC患者发生其他严重肌肉骨骼疾病概率最高（6.2%，95%CI 4.0%-9.0%）。在抗CTLA-4单药治疗中，全级别和严重腹泻的发生率在前列腺癌患者中最高（分别为41.9%，95%CI 37.9%-47.9%；14.8%，95%CI 11.5%-18.7%）。