Prior Endocrine Therapy Impact on Abiraterone Acetate Clinical Efficacy in Metastatic Castration-resistant Prostate Cancer: Post-hoc Analysis of Randomised Phase 3 Studies

Joaquim Bellmunt, Thian Kheoh, Margaret K. Yu, Matthew R. Smith, Eric J. Small, Peter F.A. Mulders, Karim Fizazi, Dana E. Rathkopf, Fred Saad, Howard I. Scher, Mary Ellen Taplin, Ian D. Davis, Dirk Schrijvers, Andrew Protheroe, Arturo Molina, Peter De Porre, Thomas W. Griffin, Johann S. De Bono, Charles J. Ryan, Stéphane Oudard

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22 Scopus citations


Background The duration of prior hormonal treatment can predict responses to subsequent therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Objective To determine if prior endocrine therapy duration is an indicator of abiraterone acetate (AA) sensitivity. Design, setting, and participants Post-hoc exploratory analysis of randomised phase 3 studies examining post-docetaxel (COU-AA-301) or chemotherapy-naïve mCRPC (COU-AA-302) patients receiving AA. The treatment effect on overall survival (OS), radiographic progression-free survival (rPFS), and prostate-specific antigen (PSA) response analysed by quartile duration of prior gonadotropin-releasing hormone agonists (GnRHa) or androgen receptor (AR) antagonist. Intervention Patients were randomised to AA (1000 mg, orally once daily) plus prednisone (5 mg, orally twice daily) or placebo plus prednisone. Prior endocrine therapy was GnRHa (COU-AA-301, n = 1127 [94%]; COU-AA-302, n = 1057 [97%], 45.1 mo or 36.7 mo median duration, respectively) and/or orchiectomy (COU-AA-301, n = 78 [7%] COU-AA-302, n = 44 [4%]); castrated patients received prior AR antagonists (COU-AA-301, n = 1015 [85%]; COU-AA-302, n = 1078 [99%], 15.7 mo or 16.1 mo median duration, respectively). Outcome measurements and statistical analysis Cox model was used to obtain hazard ratio and associated 95% confidence interval with statistical inference by log rank statistic. Results and limitations Clinical benefit with AA was observed for OS, rPFS, and PSA response for nearly all quartiles with GnRHa or AR antagonists in both COU-AA-301 and COU-AA-302. In COU-AA-301, patients with a longer duration of prior endocrine therapy tended to have greater AA OS, rPFS, and PSA response benefit, with lead-time chemotherapy bias potentially impacting COU-AA-301 results. Time to castration resistance was not captured. This analysis is limited as a post-hoc exploratory analysis. Conclusions In the COU-AA-301 and COU-AA-302 studies, AA produced clinical benefits regardless of prior endocrine therapy duration in patients with mCRPC. Patient summary Metastatic castration-resistant prostate cancer patients derived clinical benefits with abiraterone acetate regardless of prior endocrine therapy duration.

Original languageEnglish (US)
Pages (from-to)924-932
Number of pages9
JournalEuropean Urology
Issue number5
StatePublished - May 1 2016

Bibliographical note

Funding Information:
Acknowledgments: Writing assistance was provided by Ira Mills, PhD, of PAREXEL and was funded by Janssen Global Services.

Funding Information:
Funding/Support and role of the sponsor: This work was supported by Janssen Research & Development (formerly Ortho Biotech Research & Development, unit of Cougar Biotechnology). Employees of Janssen Research & Development participated in trial design and oversight, data monitoring and collection, data analysis, data interpretation, and writing of the report. The study sponsor was involved in trial design and provided grants to trial sites, but had no involvement in the conduct of the trial. Analyses done by Janssen for this report were funded by Janssen Global Services.

Publisher Copyright:
© 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.


  • Abiraterone acetate
  • Androgen receptor antagonists
  • Gonadotropin-releasing hormone
  • Prednisone
  • Prostate cancer


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