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.
Bibliographical noteFunding Information:
Financial disclosures: Joaquim Bellmunt certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: all authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Bellmunt has received honoraria and has served as a consultant for Janssen Research & Development. Kheoh, Yu, Molina, De Porre, and Griffin are employees of Janssen Research & Development and hold stock options in Johnson & Johnson. Smith served as a consultant to Janssen Research & Development. Small and Protheroe have no disclosures or potential conflicts of interest to report. Mulders has served as a consultant and has received research support from Janssen Research & Development, Astellas, and Bayer. Fizazi has participated in advisory boards and served as a speaker for Janssen. Rathkopf has received research funding from Janssen Research & Development. Saad has served as a consultant and has received research funding from Janssen Research & Development. Scher has served as an uncompensated consultant to Janssen Research & Development and reports support to Memorial Sloan Kettering Cancer Center from Janssen Research & Development related to this work. He has also served as an uncompensated consultant to AstraZeneca, Bristol Myers Squibb, Celgene, Endocyte, Exelixis, Foundation Medicine, Genentech, Medivation, Novartis, Pfizer, Takeda-Millennium and Ventana – Member of Roche; a consultant to Astellas, BIND Pharmaceuticals, Chugai Academy for Advanced Oncology, Endo/Orion Pharmaceuticals, OncologySTAT, Palmetto GBA, LLC, Sanofi Aventis, and WCG Oncology; has received an honorarium from Chugai Academy for Advanced Science; and has received support for Memorial Sloan Kettering Cancer Center from BIND Pharmaceuticals, Epic Sciences, Exelixis, and Medivation. Taplin has received institutional (Dana-Farber Cancer Institute) funding for clinical trials involving abiraterone. Davis has served as a consultant without remunerations from Janssen Research & Development, Medivation, BMS, Sanofi, Bayer, Astellas, and Ipsen. Schrijvers has participated in studies and served as a consultant and on speaker boards for Janssen Research & Development and Sanofi. de Bono is a paid employee of The Institute of Cancer Research, which has a commercial interest in abiraterone, and has served as a paid consultant for Johnson & Johnson. Ryan has received honoraria from Janssen Research & Development. Oudard has received honoraria from Janssen Research & Development.
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.
- Abiraterone acetate
- Androgen receptor antagonists
- Gonadotropin-releasing hormone
- Prostate cancer