背景:关于安全性的证据很少,功效,以及由于免疫相关不良事件(irAEs)或进行性疾病(PD)而停药后癌症患者重新启动免疫检查点抑制剂(ICI)的生存益处。这里,我们进行了一项荟萃分析,以阐明ICI再激发对癌症患者的可能益处.
方法:使用PubMed进行系统搜索,Embase,和Cochrane图书馆数据库。客观反应率(ORR),疾病控制率(DCR),无进展生存期(PFS),总生存期(OS),和irAE的发生率是感兴趣的结果。
结果:分析了涉及2026例患者的36项研究。ICI再激发与所有级别的较低发生率相关(OR,0.05;95CI,0.02-0.13,P<.05)和高等级IRAE(OR,0.37;与初始ICI治疗相比,95CI,0.21-0.64,P<.05)。尽管在ORR方面的再激发和初始治疗之间没有观察到显著差异(OR,0.69;95CI,0.39-1.20,P=.29)和DCR(OR,0.85;95CI,0.51-1.40,P=0.52),接受再激发的患者PFS改善(HR,0.56;95CI,0.43-0.73,P<0.05)和OS(HR,0.55;95CI,0.43-0.72,P<.05)比永久停止ICI治疗的患者高。亚组分析显示,对于因irAE而停止初始ICI治疗的患者,再激发显示与初始治疗相似的安全性和有效性,而对于因PD而停止ICI治疗的患者,重新激发导致高等级IRAE的发生率显着增加(OR,4.97;95CI,1.98-12.5,P<0.05)和ORR(OR,0.48;95CI,0.24-0.95,P<0.05)。
结论:ICI再激发通常是一种积极可行的策略,与相对安全性相关,类似的功效,并改善生存结果。应谨慎地单独考虑再挑战,需要随机对照试验来证实这些发现.
BACKGROUND: There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due to immune-related adverse events (irAEs) or progressive disease (PD). Here, we performed a meta-analysis to elucidate the possible benefits of ICI rechallenge in patients with cancer.
METHODS: Systematic searches were conducted using PubMed, Embase, and Cochrane Library databases. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of irAEs were the outcomes of interest.
RESULTS: Thirty-six studies involving 2026 patients were analyzed. ICI rechallenge was associated with a lower incidence of all-grade (OR, 0.05; 95%CI, 0.02-0.13, P < .05) and high-grade irAEs (OR, 0.37; 95%CI, 0.21-0.64, P < .05) when compared with initial ICI treatment. Though no significant difference was observed between rechallenge and initial treatment regarding ORR (OR, 0.69; 95%CI, 0.39-1.20, P = .29) and DCR (OR, 0.85; 95%CI, 0.51-1.40, P = 0.52), patients receiving rechallenge had improved PFS (HR, 0.56; 95%CI, 0.43-0.73, P < .05) and OS (HR, 0.55; 95%CI, 0.43-0.72, P < .05) than those who discontinued ICI therapy permanently. Subgroup analysis revealed that for patients who stopped initial ICI treatment because of irAEs, rechallenge showed similar safety and efficacy with initial treatment, while for patients who discontinued ICI treatment due to PD, rechallenge caused a significant increase in the incidence of high-grade irAEs (OR, 4.97; 95%CI, 1.98-12.5, P < .05) and a decrease in ORR (OR, 0.48; 95%CI, 0.24-0.95, P < .05).
CONCLUSIONS: ICI rechallenge is generally an active and feasible strategy that is associated with relative safety, similar efficacy, and improved survival outcomes. Rechallenge should be considered individually with circumspection, and randomized controlled trials are required to confirm these findings.