Metastatic castration-resistant prostate cancer (mCRPC) often involves bone, and bone-targeted therapy (BTT) has become part of the overall treatment strategy.
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.
This report describes the third interim analysis (prespecified at 55% overall survival [OS] events) for the COU-AA-302 trial.
Patients were grouped by concomitant BTT use or no BTT use.
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.
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.
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.
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.
ClinicalTrials.gov NCT00887198.
European urology. 2015 May 16 [Epub]
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 Small, Howard I Scher, Arturo Molina, Charles J Ryan
University of Montréal, Montréal, Québec, Canada. Electronic address: ., Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC, USA., University Hospital Leuven, Leuven, Belgium., Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA., Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA., Institute of Cancer Research and Royal Marsden Hospital, Sutton, UK., MD Anderson Cancer Center, Houston, TX, USA., University of Western Sydney School of Medicine, Ingham Institute, Liverpool, Australia., Institut Gustave Roussy, University of Paris Sud, Villejuif, France., Radboud University Medical Centre, Nijmegen, The Netherlands., Hematology and Oncology Clinics of Australia, Brisbane, Australia., Sarah Cannon Research Institute, Nashville, TN, USA., Oregon Health & Science University Knight Cancer Institute, Portland, OR, USA., Cross Cancer Institute, Edmonton, Alberta, Canada., Laval University, Québec City, Québec, Canada., Janssen Research & Development, Los Angeles, CA, USA., Janssen Research & Development, Beerse, Belgium., Janssen Research & Development, Raritan, NJ, USA., Janssen Research & Development, San Diego, CA, USA., Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA., Janssen Research & Development, Menlo Park, CA, USA.