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

Eur Urol. 2016 May;69(5):924-32. doi: 10.1016/j.eururo.2015.10.021. Epub 2015 Oct 24.


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 (1000mg, orally once daily) plus prednisone (5mg, 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.

Keywords: Abiraterone acetate; Androgen receptor antagonists; Gonadotropin-releasing hormone; Prednisone; Prostate cancer.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Abiraterone Acetate / administration & dosage
  • Androgen Receptor Antagonists / therapeutic use*
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Disease-Free Survival
  • Docetaxel
  • Double-Blind Method
  • Gonadotropin-Releasing Hormone / agonists*
  • Humans
  • Male
  • Neoplasm Metastasis
  • Orchiectomy
  • Prednisone / administration & dosage
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant / blood
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Prostatic Neoplasms, Castration-Resistant / surgery
  • Retreatment
  • Survival Rate
  • Taxoids / therapeutic use


  • Androgen Receptor Antagonists
  • Antineoplastic Agents, Hormonal
  • Taxoids
  • Docetaxel
  • Gonadotropin-Releasing Hormone
  • Prostate-Specific Antigen
  • Abiraterone Acetate
  • Prednisone