• Run-Cong Nie, Fo-Ping Chen, Shu-Qiang Yuan, Ying-Shan Luo, Shi Chen, Yong-Ming Chen, Xiao-Jiang Chen, Ying-Bo Chen, Yuan-Fang Li, and Zhi-Wei Zhou.
• Department of Gastric Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
• Eur. J. Cancer. 2019 Jan 1; 106: 1-11.

BackgroundWe aimed to assess whether the Response Evaluation Criteria in Solid Tumors (RECIST) criteria-based objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) could be valid surrogate end-points for overall survival (OS) in anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) trials.MethodsWe systematically reviewed phase 2 and phase 3 trials of anti-PD-1/PD-L1 drug trials of advanced or recurrent solid tumours that reported OS and at least one of the RECIST criteria-based end-points. We used Spearman rank correlation to evaluate the strength of the association between these end-points and OS and a linear regression model, weighted by the sample size, to assess the association between the treatment effect on these end-points and OS. We also performed sensitivity analyses and a leave-one-out cross-validation approach to evaluate the robustness of our findings.ResultsForty-three qualifying trails comprising 15,088 patients were eligible. PFS showed good correlation with OS (squared Spearman rank correlation coefficient [rs2] = 0.54; P < 0.001), while ORR and DCR illustrated moderate association with OS (rs2 = 0.29 and 0.28, respectively; both P < 0.001). The correlation was moderate between the treatment effects on PFS and OS (coefficient of determination [R2] = 0.37, P < 0.001) and poor among ORR, DCR and OS (R2 = 0.10 and 0.08, respectively); these were confirmed by sensitivity analyses (all R2 < 0.75) and the leave-one-out cross-validation approach.ConclusionsNo RECIST criteria-based end-points could be a valid surrogate for OS. At present, we proposed to set OS as the primary end-point in anti-PD-1/PD-L1 drug trials of advanced or recurrent solid tumours.Copyright © 2018 Elsevier Ltd. All rights reserved.

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