Background: Abiraterone acetate plus prednisone significantly improves radiographic progression-free survival in asymptomatic or mildly symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer compared with prednisone alone. We describe analyses of data for patient-reported pain and functional status in a preplanned interim analysis of a phase 3 trial. Methods: Between April 28, 2009, and June 23, 2010, patients with progressive, metastatic castration-resistant prostate cancer were enrolled into a multinational, double-blind, placebo-controlled trial. Patients were eligible if they were asymptomatic (score of 0 or 1 on item three of the Brief Pain Inventory Short Form [BPI-SF] questionnaire) or mildly symptomatic (score of 2 or 3) and had not previously received chemotherapy. Patients were randomly assigned (1:1) to receive oral abiraterone (1 g daily) plus prednisone (5 mg twice daily) or placebo plus prednisone in continuous 4-week cycles. Pain was assessed with the BPI-SF questionnaire, and health-related quality of life (HRQoL) with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. We analysed data with prespecified criteria for clinically meaningful pain progression and deterioration in HRQoL. All patients who underwent randomisation were included in analyses. This study is registered with ClinicalTrials.gov, number NCT00887198. Findings: 1088 patients underwent randomisation: 546 were assigned to abiraterone plus prednisone and 542 to placebo plus prednisone. At the time of the second prespecified interim analysis, median follow-up was 22·2 months (IQR 20·2-24·8). Median time to progression of mean pain intensity was longer in patients assigned to abiraterone plus prednisone (26·7 months [95% CI 19·3-not estimable]) than in those assigned to placebo plus prednisone (18·4 months [14·9-not estimable]; hazard ratio [HR] 0·82, 95% CI 0·67-1·00; p=0·0490), as was median time to progression of pain interference with daily activities (10·3 months [95% CI 9·3-13·0] vs 7·4 months [6·4-8·6]; HR 0·79, 95% CI 0·67-0·93; p=0·005). Median time to progression of worst pain was also longer with abiraterone plus prednisone (26·7 months [95% CI 19·4-not estimable]) than with placebo plus prednisone (19·4 months [16·6-not estimable]), but the difference was not significant (HR 0·85, 95% CI 0·69-1·04; p=0·109). Median time to HRQoL deterioration was longer in patients assigned to abiraterone plus prednisone than in those assigned to placebo plus prednisone as assessed by the FACT-P total score (12·7 months [95% CI 11·1-14·0] vs 8·3 months [7·4-10·6]; HR 0·78, 95% CI 0·66-0·92; p=0·003) and by the score on its prostate-cancer-specific subscale (11·1 months [8·6-13·8] vs 5·8 months [5·5-8·3]; HR 0·70, 95% CI 0·60-0·83; p<0·0001). Interpretation: Abiraterone plus prednisone delays patient-reported pain progression and HRQoL deterioration in chemotherapy-naive patients with metastatic castration-resistant prostate cancer. These results provide further support for the efficacy of abiraterone in this population. Funding: Janssen Research & Development.
Bibliographical noteFunding Information:
EB was the unpaid study chair for a clinical trial funded by Exelixis. PM has received consultancy fees from Janssen, Johnson & Johnson, AstraZeneca, Astellas Pharma, and GlaxoSmithKline. NS and MRS have served as paid advisors to and received research support from Cougar Biotechnology (now Janssen Research & Development) and Johnson & Johnson. TK, TG, SL, MLM, and AM are employees of Janssen Research & Development, and own stock in Johnson & Johnson. KF has received research support from Ortho Biotech Oncology Research (now Janssen Research & Development). CJL has received consultancy fees and travel support from Ortho Biotech Oncology Research (now Janssen Research & Development), and research support from Johnson & Johnson. DR has received research support from Ortho Biotech Oncology Research (now Janssen Research & Development). PNM and CC have received consultancy fees from Janssen Research & Development. YH is an employee of Janssen Global Services and owns stock in Johnson & Johnson. The other authors declare that they have no conflicts of interest.
This study was sponsored by Ortho Biotech Oncology Research and Development (now Janssen Research & Development), which provided research support to the investigators or their institutions while this study was done at their sites. The analyses in this paper were funded by Janssen Global Services. Writing support was provided by Dominik Wolf of PAREXEL and was funded by Janssen Global Services. We thank Margaret Rothman for constructive comments during preparation of the report.