接受免疫检查点抑制剂治疗的患者发生肾脏不良事件的比较风险：一项贝叶斯网络荟萃分析
Comparative Risk of Renal Adverse Events in Patients Receiving Immune Checkpoint Inhibitors: A Bayesian Network Meta-Analysis.
作者信息
Liu Kang, Qin Zhongke, Xu Xueqiang, Li Ting, Ge Yifei, Mao Huijuan, Xing Changying
机构信息
Department of Nephrology, Jiangsu Province Hospital (The First Affiliated Hospital of Nanjing Medical University), Nanjing, China.
出版信息
Front Oncol. 2021 Jun 16;11:662731. doi: 10.3389/fonc.2021.662731. eCollection 2021.
BACKGROUND
Immune checkpoint inhibitors (ICIs) have brought a paradigm shift to cancer treatment. However, little is known about the risk of renal adverse events (RAEs) of ICI-based regimens, especially ICI combination therapy.
METHODS
We carried out a network meta-analysis of randomized controlled trials (RCTs) to compare the risk of RAEs between ICI-based regimens and traditional cancer therapy, including chemotherapy and targeted therapy. Subgroup analysis was conducted based on tumor types.
RESULTS
Ninety-five eligible RCTs involving 40,552 participants were included. The overall incidence of RAEs, grade 3-5 RAEs, acute kidney injury (AKI), and grade 3-5 AKI was 4.3%, 1.2%, 1.3%, and 0.8%, respectively. Both ICI-based treatment regimens and traditional cancer therapy showed significantly higher risk of RAEs and AKI than the placebo. Among ICI monotherapy, anti-PD-1 (RR: 0.51, 95%CI: 0.29-0.91) was significantly safer than anti-CTLA-4 in terms of RAEs. Anti-CTLA-4 showed significantly higher toxicity than anti-PD-1 (RR: 0.33, 95%CI: 0.14-0.77), anti-PD-L1 (RR: 0.38, 95%CI:0.16-0.91), and anti-PD-1 plus anti-CTLA-4 (RR: 0.32, 95%CI: 0.12-0.87) in terms of grade 3-5 RAEs. The difference was not significant between ICI monotherapy and traditional cancer therapy, except that targeted therapy seemed the least toxic therapy in terms of the incidence of AKI. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1 (RR: 1.61, 95%CI: 1.02-2.56). The difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICI plus chemotherapy showed increased risk of both RAEs and AKI compared with ICI monotherapy, chemotherapy, and targeted therapy. The overall results remained robust in the meta-regression and sensitivity analyses.
CONCLUSIONS
Among ICI monotherapy, anti-CTLA-4 appeared to be associated with increased toxicity, especially in terms of grade 3-5 RAEs. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1. However, the difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICIs plus chemotherapy seemed to be the most toxic treatment regimen in terms of RAEs, AKI, and grade 3-5 AKI.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42020197039.
背景
免疫检查点抑制剂（ICIs）给癌症治疗带来了范式转变。然而，对于基于ICI的治疗方案，尤其是ICI联合治疗，其导致肾脏不良事件（RAEs）的风险知之甚少。
方法
我们对随机对照试验（RCTs）进行了网络荟萃分析，以比较基于ICI的治疗方案与传统癌症治疗（包括化疗和靶向治疗）之间发生RAEs的风险。基于肿瘤类型进行了亚组分析。
结果
纳入了95项符合条件的RCTs，涉及40552名参与者。RAEs、3 - 5级RAEs、急性肾损伤（AKI）和3 - 5级AKI的总体发生率分别为4.3%、1.2%、1.3%和0.8%。与安慰剂相比，基于ICI的治疗方案和传统癌症治疗均显示出更高的RAEs和AKI风险。在ICI单药治疗中，就RAEs而言，抗PD - 1（风险比：0.51，95%置信区间：0.29 - 0.91）比抗CTLA - 4显著更安全。就3 - 5级RAEs而言，抗CTLA - 4显示出比抗PD - 1（风险比：0.33，95%置信区间：0.14 - 0.77）、抗PD - L1（风险比：0.38，95%置信区间：0.16 - 0.91）和抗PD - 1加抗CTLA - 4（风险比：0.32，95%置信区间：0.12 - 0.87）更高的毒性。除了在AKI发生率方面靶向治疗似乎是毒性最小的治疗方法外，ICI单药治疗与传统癌症治疗之间的差异不显著。抗CTLA - 4加抗PD - 1与抗PD - 1相比，RAEs风险更高（风险比：1.61，95%置信区间：1.02 - 2.56）。在RAEs和AKI方面，其他双联ICI方案与ICI单药治疗之间的差异不显著。与ICI单药治疗、化疗和靶向治疗相比，ICI加化疗显示出RAEs和AKI风险均增加。在荟萃回归和敏感性分析中，总体结果仍然稳健。
结论
在ICI单药治疗中，抗CTLA - 4似乎与毒性增加有关，尤其是在3 - 5级RAEs方面。抗CTLA - 4加抗PD - 1与抗PD - 1相比，RAEs风险更高。然而，在RAEs和AKI方面，其他双联ICI方案与ICI单药治疗之间的差异不显著。就RAEs、AKI和3 - 5级AKI而言，ICI加化疗似乎是毒性最大的治疗方案。
系统评价注册
PROSPERO，标识符CRD42020197039。
Zotero 插件