753O - Final overall survival (OS) analysis of COU-AA-302, a randomized phase 3 study of abiraterone acetate (AA) in metastatic castration-resistant prost...

Date 28 September 2014
Event ESMO 2014
Session Genitourinary tumours, prostate 1
Topics Anticancer Agents
Prostate Cancer
Biological Therapy
Presenter Ira Mills
Citation Annals of Oncology (2014) 25 (suppl_4): iv255-iv279. 10.1093/annonc/mdu336
Authors C.J. Ryan1, M.R. Smith2, K. Fizazi3, K. Miller4, P. Mulders5, C.N. Sternberg6, F. Saad7, T. Griffin8, P. De Porre9, Y.C. Park10, J. Li11, T. Kheoh12, V. Naini8, A. Molina13, D.E. Rathkopf14
  • 1Department Of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, 94115 - San Francisco/US
  • 2Hematology-oncology, Harvard Medical School and Massachusetts General Hospital Cancer Center, Boston/US
  • 3Department Of Cancer Medicine, Institut Gustave Roussy, University of Paris Sud, Villejuif/FR
  • 4Department Of Urology, Charité Berlin, Berlin/DE
  • 5Department Of Urology, Radboud University Medical Centre, Nijmegen/NL
  • 6Department Of Medical Oncology, San Camillo and Forlanini Hospitals, Rome/IT
  • 7Surgery, University of Montréal, Montréal/CA
  • 8Wc Clinical Oncology, Janssen Research & Development, Los Angeles/US
  • 9Oncology Development, Janssen Research & Development, Beerse/BE
  • 10Biostatistics, Janssen Research & Development, Raritan/US
  • 11Pap, Janssen Research & Development, Raritan/US
  • 12Biostatistics, Janssen Research & Development, Los Angeles/US
  • 13Oncology Ta Admin Pa, Janssen Research & Development, Menlo Park/US
  • 14Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York/US



AA is a prodrug of abiraterone, a selective CYP17 inhibitor that blocks androgen biosynthesis and is approved, with prednisone (P), for the treatment of pts with progressive mCRPC. Planned interim analyses of COU-AA-302 (at 13%, 43%, and 56% death events) in mCRPC chemotherapy-naïve pts showed that AA + P significantly delayed disease progression and improved OS compared with P alone, and was well tolerated.1,2 Herein, we report the pre-specified final analysis (96% of planned death events) OS and safety outcomes.


Pts (N = 1088) were randomized 1:1 to receive AA (1 g) + P (5 mg po BID) vs P. Co-primary end points were radiographic progression-free survival and OS. Median time to events with 95% CI was estimated using the Kaplan-Meier method. Cox model was used to estimate the hazard ratio (HR). Stratified log-rank test was used to test the difference in treatment effect. The O'Brien-Fleming boundary using the Lan-DeMets α-spending function was implemented to control the overall α at 0.04 for OS. For this final analysis, the nominal significance level for efficacy is 0.0384.


With median follow-up of 49.4 mos at final analysis, 741 deaths were observed. 44% of pts in the P arm subsequently received AA + P. AA + P significantly prolonged OS vs P (median OS, 34.7 vs 30.3 mos; HR = 0.80 [95% CI, 0.69-0.93]; p = 0.0027). AEs of special interest were more common with AA + P vs P; grade 3/4 AEs: hypertension, 4.6% vs 3.1%; hypokalemia, 2.6% vs 1.9%; ALT increased, 5.9% vs 0.7%; AST increased, 3.3% vs 0.9%; fluid retention/edema, 1.1% vs 1.7%.


With a median follow-up of more than 4 years, the COU-AA-302 pre-specified, final analysis demonstrates a statistically significant OS benefit with AA + P even though a large number of pts in the P arm received AA + P and other subsequent therapy. With nearly an additional 2 years of follow-up since last reported, AA + P maintains a favorable safety profile and is well tolerated. 1. Ryan CJ et al. NEJM. 2013;368:138-148. 2. Rathkopf DE et al. Eur Urol. 2014 March 6 [Epub ahead of print].


C.J. Ryan: has received honoraria from Janssen; M.R. Smith: has served as a consultant/advisor to and received research funding from Janssen; K. Fizazi: has served as a consultant/advisor to and received honoraria from Janssen; K. Miller: has served as an advisor to Janssen, Medivation, Astellas, Novartis, Merck, Amgen, Bayer, BMS, Dendreon, and Pfizer; C.N. Sternberg: has received honoraria from Astellas, Johnson & Johnson, Ipsen, Bayer, and Millennium; F. Saad: has served as a consultant/advisor to and received honoraria and research funding from Astellas and Janssen;T. Griffin, P. De Porre, Y.C. Park, J. Li and T. Kheoh: is an employee of Janssen and owns stock in Johnson & Johnson;V. Naini: is an employee of Janssen;A. Molina: is an employee of Janssen and owns stock in Johnson & Johnson;D.E. Rathkopf: has served as a consultant/advisor to Johnson & Johnson and has received research funding (uncompensated) from Celgene, Janssen/J&J, Medivation/Astellas, Millennium, and Novartis. All other authors have declared no conflicts of interest.