Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302)

Dana E. Rathkopf, Matthew R. Smith, Johann S. De Bono, Christopher J. Logothetis, Neal D. Shore, Paul De Souza, Karim Fizazi, Peter F.A. Mulders, Paul Mainwaring, John D. Hainsworth, Tomasz M. Beer, Scott North, Yves Fradet, Hendrik Van Poppel, Joan Carles, Thomas W. Flaig, Eleni Efstathiou, Evan Y. Yu, Celestia S. Higano, Mary Ellen TaplinThomas W. Griffin, Mary B. Todd, Margaret K. Yu, Youn C. Park, Thian Kheoh, Eric J. Small, Howard I. Scher, Arturo Molina, Charles J. Ryan, Fred Saad

Research output: Contribution to journalArticlepeer-review

254 Scopus citations


Outcome measurements and statistical analysis: Co-primary end points were radiographic progression-free survival (rPFS) and overall survival (OS). Median times to event outcomes were estimated using the Kaplan-Meier method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were derived using the Cox model, and treatment comparison used the log-rank test. The O'Brien-Fleming Lan-DeMets a-spending function was used for OS. Adverse events were summarised descriptively. Results and limitations: With a median follow-up duration of 27.1 mo, improvement in rPFS was statistically significant with abiraterone treatment versus prednisone (median: 16.5 vs 8.2 mo; HR: 0.52 [95% CI, 0.45-0.61]; p < 0.0001). Abiraterone improved OS (median: 35.3 vs 30.1 mo; HR: 0.79 [95% CI, 0.66-0.95]; p = 0.0151) but did not reach the prespecified statistical efficacy boundary (a-level: 0.0035). A post hoc multivariate analysis for OS using known prognostic factors supported the primary results (HR: 0.74 [95% CI, 0.61-0.89]; p = 0.0017), and all clinically relevant secondary end points and patient-reported outcomes improved. While the post hoc nature of the long-term safety analysis is a limitation, the safety profile with longer treatment exposure was consistent with prior reports.

Conclusions: The updated IA of study COU-AA-302 in patients with mCRPC without prior chemotherapy confirms that abiraterone delays disease progression, pain, and functional deterioration and has clinical benefit with a favourable safety profile, including in patients treated for ≥ 24 mo.

Trial registration: Study COU-AA-302, ClinicalTrials.gov number, NCT00887198. Patient summary: The updated results of this ongoing study showed that disease progression was delayed in patients with advanced prostate cancer who were treated with abiraterone acetate and prednisone, and there was a continued trend in prolongation of life compared with patients treated with prednisone alone. Treatment with abiraterone acetate and prednisone was well tolerated by patients who were treated for >2 yr.

Background: Abiraterone acetate (an androgen biosynthesis inhibitor) plus prednisone is approved for treating patients with metastatic castration-resistant prostate cancer (mCRPC). Study COU-AA-302 evaluated abiraterone acetate plus prednisone versus prednisone alone in mildly symptomatic or asymptomatic patients with progressive mCRPC without prior chemotherapy.

Objective: Report the prespecified third interim analysis (IA) of efficacy and safety outcomes in study COU-AA-302.

Design, setting, and participants: Study COU-AA-302, a double-blind placebo-controlled study, enrolled patientswithmCRPC fromApril 2009 to June 2010. A total of 1088 patients were stratified by Eastern Cooperative Oncology Group performance status (0 vs 1). Intervention: Patients were randomised 1:1 to abiraterone 1000 mg plus prednisone 5 mg twice daily by mouth versus prednisone.

Original languageEnglish (US)
Pages (from-to)815-825
Number of pages11
JournalEuropean Urology
Issue number5
StatePublished - Nov 1 2014

Bibliographical note

Publisher Copyright:
© 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.


  • Abiraterone acetate
  • Chemotherapy-naive
  • Efficacy
  • Metastatic castration-resistant
  • Safety
  • prostate cancer


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