Evaluation of potential surrogate endpoints for prediction of overall survival in patients with castration-resistant prostate cancer: trial-level meta-analysis
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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.
KeywordsSurrogate endpoint Overall survival Meta-analysis Castration-resistant prostate cancer Chemotherapy Androgen-targeting therapy
We thank Dr. Jia Ji (Johnson & Johnson) and Dr. Shanshan Bi (Pfizer) for their kind suggestions.
The views expressed in this paper are those of the authors and do not necessarily represent those of the China National Medical Products Administration.
Chen WJ, Li L, Zhou TY, Lu W, Ji SM, and Song XY designed the research; Chen WJ, Li L, and Ji SM performed the research; Chen WJ, Li L, and Song XY analyzed the data; Chen WJ, Li L, and Zhou TY wrote the article.
This work was supported by the National Natural Science Foundation of China [Grant No. 81302831].
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