PD1/PD-L1免疫检查点抑制剂(ICIs)已经彻底改变了癌症治疗。虽然在ICI环境中使用代用终点预测总生存期(OS)的准确性存在争议，但这些端点通常在确认性试验中使用。本文旨在探讨ICIs和化疗(CT)结合治疗一线环境下的经典和新的代理端点的有效性。我们进行系统综述以确定调查抗PD1/PD-L1药物与单独CT相比的RCTs。我们执行(i)以评估中位生存期(mOS)的预测因子和(ii)比较级别分析来预测OS风险比(HR)。拟合由试验规模加权的线性回归模型，并报告调整后的R2值。满足纳入标准的39个RCT涉及22,341名患者(17个非小细胞肺癌，9个胃食管癌和13个其他癌症)，涉及十种不同的ICI。总体而言，ICI plus CT改善了OS(HR=0.76;95％CI：0.73-0.80)。在单臂水平分析中，将中位反应持续时间和ORR(中位持续时间-ORR)组合在一起得到了最佳的mOS预测结果，并且中位PFS(R2=0.5)。在比较级别分析中，PFS HR与OS HR有中度相关性(R2=0.52)。早期OS读数与最终OS结果高度相关(R2=0.80)。一线RCT中代理端点与OS之间的关联是中低的。早期的OS结果预示着最终的OS HR，而mDOR-ORR端点可帮助更好地设计单臂II期试验之后的确认性试验。

PD1/PD-L1 immune checkpoint inhibitors (ICI) have revolutionized cancer treatment. Although there is controversy about the accuracy of surrogate endpoints in the ICI setting to predict overall survival (OS), these endpoints are commonly used in confirmatory trials. Here we aimed to explore the validity of classical and novel surrogate endpoints in randomised controlled trials (RCT) that combine ICI plus chemotherapy (CT) in the first-line setting.A systematic review was conducted to identify RCT investigating anti-PD1/PD-L1 drugs plus CT versus CT alone. We performed (i) arm-level analysis to evaluate predictors of median OS (mOS) and (ii) comparison-level analysis for OS hazard ratio (HR) estimations. Linear regression models weighted by trial size were fitted and adjusted R2 values were reported.Thirty-nine RCTs involving 22,341 patients met the inclusion criteria (17 non-small cell lung, 9 gastroesophageal and 13 in other cancers) with ten different ICI under study. Overall, ICI plus CT improved OS (HR = 0.76; 95%CI: 0.73-0.80). In the arm-level analysis, the best mOS prediction was obtained with a new endpoint that combines median duration of response and ORR (mDoR-ORR) and with median PFS (R2 = 0.5 both). In the comparison-level analysis, PFS HR showed a moderate association with OS HR (R2 = 0.52). Early OS read-outs were highly associated with final OS outcomes (R2 = 0.80).The association between surrogate endpoints and OS in first-line RCT combining anti-PD1/PD-L1 and CT is moderate-low. Early OS read-outs showed a good association with final OS HR while the mDOR-ORR endpoint could help to better design confirmatory trials after single-arm phase II trials.Copyright © 2023 Elsevier Ltd. All rights reserved.