Background: Abiraterone acetate improved overall survival in metastatic castration-resistant prostate cancer at a preplanned interim analysis of the COU-AA-301 double-blind, placebo-controlled phase 3 study. Here, we present the final analysis of the study before crossover from placebo to abiraterone acetate (after 775 of the prespecified 797 death events).
Methods: Between May 8, 2008, and July 28, 2009, this study enrolled 1195 patients at 147 sites in 13 countries. Patients were eligible if they had metastatic castration-resistant prostate cancer progressing after docetaxel. Patients were stratified according to baseline Eastern Cooperative Oncology Group (ECOG) performance status, worst pain over the past 24 h on the Brief Pain Inventory-Short Form, number of previous chemotherapy regimens, and type of progression. Patients were randomly assigned (ratio 2:1) to receive either abiraterone acetate (1000 mg, once daily and orally) plus prednisone (5 mg, orally twice daily) or placebo plus prednisone with a permuted block method via an interactive web response system. The primary endpoint was overall survival, analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00091442.
Findings: Of the 1195 eligible patients, 797 were randomly assigned to receive abiraterone acetate plus prednisone (abiraterone group) and 398 to receive placebo plus prednisone (placebo group). At median follow-up of 20·2 months (IQR 18·4—22·1), median overall survival for the abiraterone group was longer than in the placebo group (15·8 months [95% CI 14·8—17·0] vs 11·2 months [10·4—13·1]; hazard ratio [HR] 0·74, 95% CI 0·64—0·86; p<0·0001). Median time to PSA progression (8·5 months, 95% CI 8·3—11·1, in the abiraterone group vs 6·6 months, 5·6—8·3, in the placebo group; HR 0·63, 0·52—0·78; p<0·0001), median radiologic progression-free survival (5·6 months, 5·6—6·5, vs 3·6 months, 2·9—5·5; HR 0·66, 0·58—0·76; p<0·0001), and proportion of patients who had a PSA response (235 [29·5%] of 797 patients vs 22 [5·5%] of 398; p<0·0001) were all improved in the abiraterone group compared with the placebo group. The most common grade 3—4 adverse events were fatigue (72 [9%] of 791 patients in the abiraterone group vs 41 [10%] of 394 in the placebo group), anaemia (62 [8%] vs 32 [8%]), back pain (56 [7%] vs 40 [10%]), and bone pain (51 [6%] vs 31 [8%]).
Interpretation: This final analysis confirms that abiraterone acetate significantly prolongs overall survival in patients with metastatic castration-resistant prostate cancer who have progressed after docetaxel treatment. No new safety signals were identified with increased follow-up.
Funding: Janssen Research & Development.
Written by:
Prof Dr Karim Fizazi MD, Prof Howard I Scher MD, Arturo Molina MD, Prof Christopher J Logothetis MD, Kim N Chi MD, Robert J Jones PhD, John N Staffurth MD, Scott North MD, Nicholas J Vogelzang MDj, Prof Fred Saad MD, Paul Mainwaring MDl, Stephen Harland MD, Oscar B Goodman MD, Cora N Sternberg MD, Jin Hui Li PhD, Thian Kheoh PhD, Christopher M Haqq MD, Prof Johann S de Bono MB ChB, for the COU-AA-301 Investigators Are you the author?
Reference: The Lancet Oncology, Early Online Publication, 18 September 2012
doi: 10.1016/S1470-2045(12)70379-0
