Meta-analyses evaluating surrogate endpoints for overall survival in cancer randomized trials: A critical review

Publication date: Available online 23 November 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Marion Savina, Sophie Gourgou, Antoine Italiano, Derek Dinart, Virginie Rondeau, Nicolas Penel, Simone Mathoulin-Pelissier, Carine Bellera
BackgroundIn cancer randomized controlled trials (RCT), alternative endpoints are increasingly being used in place of overall survival (OS) to reduce sample size, duration and cost of trials. It is necessary to ensure that these endpoints are valid surrogates for OS. We aimed at identifying meta-analyses evaluating surrogate endpoints and assessing the strength of evidence for each study.Materials and methodsWe performed a systematic review to identify meta-analyses of cancer RCTs assessing surrogate endpoints for OS. We evaluated the strength of the association between the endpoints based on (i) the Institute of Quality and Efficiency in Health Care guidelines and (ii) the Biomarker-Surrogate Evaluation Schema.Results53 publications reported on 164 meta-analyses, with heterogeneous statistical methods Disease-free survival (DFS) and progression-free survival showed good surrogacy properties for OS in colorectal cancer, lung cancer and head and neck cancer. DFS was also highly correlated to OS in gastric cancer.Conclusion(s)Clinical settings with validated surrogate endpoints for OS remain limited. Harmonization of the statistical methodology used to evaluate surrogate endpoints is required.



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