摘要
Abstract
Immune checkpoint inhibitors(ICIs)have revolutionized cancer therapy,but their use is frequently complicated by immune-related adverse events(irAEs),which often require management with corticosteroids or additional immunosuppressive agents.The prognostic impact of these therapeutic strategies in the setting of irAEs has not been systematically elucidated.This systematic review and meta-analysis aimed to evaluate the impact of corticosteroid(CS)and second-line immunosuppressant(IM)use on survival outcomes among patients who developed irAEs during ICI therapy.Following a preregistered protocol(PROSPERO CRD1144835),we systematically searched PubMed,Embase,Web of Science,Cochrane Library,SinoMed,CNKI and Wanfang to identify studies published in the past 10 years(up to May 2025)reporting on the association between CS and IM use and survival outcomes in ICI-treated patients with irAEs.Two reviewers independently performed study selection,data extraction,and quality assessment.Meta-analyses were performed using R software.A total of 11 studies comprising 7 255 patients were included.Meta-analysis showed that CS use versus no use was not significantly associated with overall survival(OS)(HR=0.73,95%CI:0.45-1.18)or progression-free survival(PFS)(HR=0.68,95%CI:0.00-98.01).For post-irAE survival outcomes,higher cumulative CS dose(per 1 000 mg increment)was associated with a mild protective effect on post-irAE OS(HR=0.95,95%CI:0.92-0.98)and post-irAE PFS(HR=0.96,95%CI:0.94-0.99).In contrast to CS alone,IM use in combination with CS was associated with significantly increased risk of disease progression or death for post-irAE OS(HR=1.40,95%CI:1.11-1.76)and post-irAE PFS(HR=1.32,95%CI:1.08-1.62).Sensitivity analyses demonstrated good robustness of the main significant results.Current evidence suggests that CS and IM management strategies may differentially affect survival outcomes in patients with irAEs following ICI therapy.Increased cumulative CS dose is not associated with worse outcomes,whereas the addition of second-line IMs may increase the risk of adverse survival outcomes.Further prospective studies are warranted to optimize irAE management strategies and to balance the risks of immunosuppressive therapy with anticancer efficacy.关键词
免疫检查点抑制剂/免疫相关不良事件/糖皮质激素/免疫抑制剂/生存结局/Meta分析/系统评价Key words
Immune checkpoint inhibitors/Immune-related adverse events/corticosteroids/Immunosuppressants/Survival outcomes/Meta-analysis/Systematic review分类
医药卫生
