European Journal of Clinical Pharmacology

, Volume 75, Issue 11, pp 1521–1532 | Cite as

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

  • Wenjun Chen
  • Liang LiEmail author
  • Shuangmin Ji
  • Xuyang Song
  • Wei Lu
  • Tianyan ZhouEmail author



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.


Surrogate 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.

Authors’ contributions

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].

Supplementary material

228_2019_2736_MOESM1_ESM.docx (88 kb)
ESM 1 (DOCX 88 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, Department of Pharmaceutics, School of Pharmaceutical SciencesPeking UniversityBeijingChina
  2. 2.Center for Drug EvaluationNational Medical Products AdministrationBeijingChina
  3. 3.Department of Pharmaceutics, College of PharmacyUniversity of FloridaGainesvilleUSA

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