Impact of bone-targeted therapies in chemotherapy-naïve metastatic castration-resistant prostate cancer patients treated with abiraterone acetate: Post hoc analysis of study COU-AA-302

Fred Saad, Neal Shore, Hendrik Van Poppel, Dana E. Rathkopf, Matthew R. Smith, Johann S. De Bono, Christopher J. Logothetis, Paul De Souza, Karim Fizazi, Peter F.A. Mulders, Paul Mainwaring, John D. Hainsworth, Tomasz M. Beer, Scott North, Yves Fradet, Thomas A. Griffin, Peter De Porre, Anil Londhe, Thian Kheoh, Eric J. SmallHoward I. Scher, Arturo Molina, Charles J. Ryan

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Background Metastatic castration-resistant prostate cancer (mCRPC) often involves bone, and bone-targeted therapy (BTT) has become part of the overall treatment strategy. Objective Investigation of outcomes for concomitant BTT in a post hoc analysis of the COU-AA-302 trial, which demonstrated an overall clinical benefit of abiraterone acetate (AA) plus prednisone over placebo plus prednisone in asymptomatic or mildly symptomatic chemotherapy-naïve mCRPC patients. Design, setting, and participants This report describes the third interim analysis (prespecified at 55% overall survival [OS] events) for the COU-AA-302 trial. Intervention Patients were grouped by concomitant BTT use or no BTT use. Outcome measurements and statistical analysis Radiographic progression-free survival and OS were coprimary end points. This report describes the third interim analysis (prespecified at 55% OS events) and involves patients treated with or without concomitant BTT during the COU-AA-302 study. Median follow-up for OS was 27.1 mo. Median time-to-event variables with 95% confidence intervals (CIs) were estimated using the Kaplan-Meier method. Adjusted hazard ratios (HRs), 95% CIs, and p values for concomitant BTT versus no BTT were obtained via Cox models. Results and limitations While the post hoc nature of the analysis is a limitation, superiority of AA and prednisone versus prednisone alone was demonstrated for clinical outcomes with or without BTT use. Compared with no BTT use, concomitant BTT significantly improved OS (HR 0.75; p = 0.01) and increased the time to ECOG deterioration (HR 0.75; p < 0.001) and time to opiate use for cancer-related pain (HR 0.80; p = 0.036). The safety profile of concomitant BTT with AA was similar to that reported for AA in the overall intent-to-treat population. Osteonecrosis of the jaw (all grade 1/2) with concomitant BTT use was reported in <3% of patients. Conclusions AA with concomitant BTT was safe and well tolerated in men with chemotherapy-naïve mCRPC. The benefits of AA on clinical outcomes were increased with concomitant BTT. Patient summary Treatment of advanced prostate cancer often includes bone-targeted therapy. This post hoc analysis showed that in patients with advanced prostate cancer who were treated with abiraterone acetate and prednisone in combination with bone-targeted therapy, there was a continued trend in prolongation of life when compared with patients treated with prednisone alone. Trial registration NCT00887198.

Original languageEnglish (US)
Pages (from-to)570-577
Number of pages8
JournalEuropean Urology
Issue number4
StatePublished - Oct 1 2015

Bibliographical note

Funding Information:
Funding/Support and role of the sponsor: This work was supported by Janssen Research & Development (formerly Ortho Biotech Oncology Research & Development, unit of Cougar Biotechnology). Writing assistance was provided by Ann P. Tighe of PAREXEL and was funded by Janssen Global Services, LLC. The sponsor played a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript.

Publisher Copyright:
© 2015 European Association of Urology.


  • Abiraterone acetate
  • Bone-targeted therapy
  • Chemotherapy-naïve
  • Metastatic castration-resistant prostate cancer


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