Department of Radiation Oncology, Wuzhou Red Cross Hospital, 3-1 Xinxing First Road, Wuzhou, 543001, People's Republic of China.
Department of Medical Oncology, Wuzhou Red Cross Hospital, 3-1 Xinxing First Road, Wuzhou, 543001, People's Republic of China.
Sci Rep. 2020 Sep 23;10(1):15567. doi: 10.1038/s41598-020-72649-5.
This study aimed to describe the landscape of Immune checkpoint inhibitors (ICIs)-related adverse events (AEs) in a predominantly Chinese cohort. We searched electronic datasets including PubMed, Web of Science and Embase to identify and recruit relevant trials up to September 2, 2019. Clinical trials focusing on ICIs in Chinese patients or a predominantly Chinese population were included. Incidences of treatment-related AEs (TRAEs) and immune-related AEs (irAEs) were pooled and compared. In total, we recruited 13 trials consisting of 1063 patients, with 922 (86.7%) receiving ICI monotherapy and 141 (13.3%) receiving combination of ICI with chemotherapy or anti-angiogenesis. The pooled incidence of any grade TRAEs, grade 1-2, grade 3-5 TRAEs, any grade irAEs, grade 1-2 irAEs and grade 3-5 irAEs in all 1063 patients were 84.1%, 63.3%, 20.9%, 43.3%, 40.0% and 3.0%, respectively. Moreover, 4.3% (44/1018) of patients experienced treatment discontinuation and only 8 (0.8%) patients experienced treatment-related death. Compared to ICI monotherapy, combination significantly increased grade 3-5 TRAEs (46.1% vs. 17.0%, P < 0.001) and grade 3-5 irAEs (7.1% vs. 2.0%, P = 0.015). By comparing the toxicity profiles between different ICIs, we found some drug-specific AEs such as reactive capillary haemangiomas for camrelizumab (58.6%), hyperglycemia for toripalimab (55.6%) and pyrexia for tislelizumab (54.3%). Additionally, nivolumab has the lowest incidence of any grade (64.1%) and grade 3-5 (11.8%) TRAEs. ICI-related AEs were generally mild and tolerable for a predominantly Chinese cohort. However, we should pay attention to the combination of ICI with chemotherapy as it could increase grade 3-5 TRAEs and irAEs.
本研究旨在描述以中国人为主的队列中免疫检查点抑制剂(ICI)相关不良事件(AE)的概况。我们检索了包括 PubMed、Web of Science 和 Embase 在内的电子数据库,以确定并招募截至 2019 年 9 月 2 日相关的临床试验。纳入了专注于中国患者或主要为中国人的 ICI 的临床试验。汇总并比较了治疗相关 AE(TRAEs)和免疫相关 AE(irAEs)的发生率。共纳入 13 项临床试验,共纳入 1063 例患者,922 例(86.7%)接受 ICI 单药治疗,141 例(13.3%)接受 ICI 联合化疗或抗血管生成药物治疗。所有 1063 例患者的任何级别 TRAEs、1-2 级 TRAEs、3-5 级 TRAEs、任何级别 irAEs、1-2 级 irAEs 和 3-5 级 irAEs 的发生率分别为 84.1%、63.3%、20.9%、43.3%、40.0%和 3.0%。此外,4.3%(44/1018)的患者因治疗而停药,仅 8 例(0.8%)患者因治疗相关死亡。与 ICI 单药治疗相比,联合治疗显著增加了 3-5 级 TRAEs(46.1% vs. 17.0%,P < 0.001)和 3-5 级 irAEs(7.1% vs. 2.0%,P = 0.015)。通过比较不同 ICI 的毒性谱,我们发现了一些药物特异性 AE,如卡瑞利珠单抗的反应性毛细血管血管瘤(58.6%)、特瑞普利单抗的高血糖症(55.6%)和替雷利珠单抗的发热(54.3%)。此外,纳武利尤单抗的任何级别(64.1%)和 3-5 级(11.8%)TRAEs 发生率最低。对于以中国人为主的队列,ICI 相关 AE 通常为轻度和可耐受的。然而,我们应该注意 ICI 与化疗的联合应用,因为它可能会增加 3-5 级 TRAEs 和 irAEs 的发生。