Evaluation of potential surrogate endpoints for prediction of overall survival in patients with castration-resistant prostate cancer: trial-level meta-analysis.

Abstract

Overall survival (OS) has traditionally been the primary endpoint to evaluate drug efficiency in oncology but is often limited by the long observation period and high cost. The aims of this study were to perform a comprehensive meta-analysis at a clinical trial level to investigate the potential surrogate endpoints of OS in patients with castration-resistant prostate cancer (CRPC), and to predict OS based on the relationships associated with the potential surrogate endpoints. A systematic literature search was conducted in the PubMed database up to August 2018. Correlations between OS and potential surrogate endpoints were determined by linear regression analysis weighted by the square roots of sample size. Simulations were conducted to assess the effect of covariates on the relationships between OS and surrogate endpoints. A total of 233 studies including clinical trials and real-world data were included in our dataset. The correlations between median OS and potential surrogate endpoints for androgen-targeting therapy (R2 = 0.58-0.92) were generally stronger than those for taxane chemotherapy (R2 = 0.37-0.71). Median radiographic progression-free survival (rPFS) showed the strongest correlations with median OS (R2 = 0.94) in patients treated with novel androgen-targeting therapy. The meta-analysis demonstrated that rPFS might serve as a potential surrogate endpoint of OS and offer opportunity to facilitate the interim analyses and decision-making during the early stage of clinical trials for androgen-targeting agents.