Document Detail


Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study.
MedLine Citation:
PMID:  22995653     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Karim Fizazi; Howard I Scher; Arturo Molina; Christopher J Logothetis; Kim N Chi; Robert J Jones; John N Staffurth; Scott North; Nicholas J Vogelzang; Fred Saad; Paul Mainwaring; Stephen Harland; Oscar B Goodman; Cora N Sternberg; Jin Hui Li; Thian Kheoh; Christopher M Haqq; Johann S de Bono;
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Publication Detail:
Type:  Clinical Trial, Phase III; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2012-09-18
Journal Detail:
Title:  The Lancet. Oncology     Volume:  13     ISSN:  1474-5488     ISO Abbreviation:  Lancet Oncol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-02     Completed Date:  2012-12-07     Revised Date:  2014-08-18    
Medline Journal Info:
Nlm Unique ID:  100957246     Medline TA:  Lancet Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  983-92     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00638690
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Androstadienes / therapeutic use*
Castration
Double-Blind Method
Humans
Male
Middle Aged
Neoplasm Metastasis
Orchiectomy
Prostatic Neoplasms / drug therapy*,  mortality,  pathology
Chemical
Reg. No./Substance:
0/Androstadienes; 154229-18-2/17-(3-pyridyl)-5,16-androstadien-3beta-acetate
Investigator
Investigator/Affiliation:
M Alam / ; M Brown / ; P Clingan / ; A Costello / ; I Davis / ; P de Souza / ; L Horvath / ; P Inglis / ; R Lynch / ; P Mainwaring / ; G Marx / ; S Ng / ; L Nott / ; F Parnis / ; C Steer / ; G Van Hazel / ; S Wong / ; G Janetschek / ; W Loidl / ; M Marberger / ; D Luyten / ; J Machiels / ; V Renard / ; S Rottey / ; B Sautois / ; P Schöffski / ; D Schrijvers / ; F Van Aelst / ; P Werbrouck / ; W Wynendaele / ; T Cheng / ; K Chi / ; S Ellard / ; S Ernst / ; S Hotte / ; M Jancewicz / ; L Klotz / ; J Michels / ; S North / ; R Rajan / ; F Saad / ; L Wood / ; S Yadav / ; S Abadie / ; K Fizazi / ; A Fléchon / ; F Joly / ; R Kaplan / ; I Krakowski / ; S Oudard / ; F Rolland / ; S Zanetta / ; K Miller / ; D Pfister / ; M Stöckle / ; H Suttmann / ; M Wirth / ; Z Faluhelyi / ; C Salamon / ; M Wenczl / ; R Algeri / ; C Boni / ; C Cianci / ; P Conte / ; C Sternberg / ; E Villa / ; P Mulders / ; B Bird / ; O Breathnach / ; J McCaffrey / ; R McDermott / ; S O'Reilly / ; J Bellmunt / ; I Duran Martinez / ; A Font Pous / ; E Gallardo / ; J Germa Lluch / ; I Gil Bazo / ; A Gonzalez del Alba / ; B Mellado Gonzalez / ; J deBono / ; G Durkan / ; P Elliot / ; S Harland / ; P Hoskin / ; N James / ; R Jones / ; H Patterson / ; A Protheroe / ; J Staffurth / ; J O'Sullivan / ; J Waxman / ; M Aklilu / ; L Appelman / ; E Arrowsmith / ; V Assikis / ; A Baron / ; W Berry / ; J Burke / ; J Carney / ; L Chu / ; N Cohen / ; T Cosgriff / ; E Crane / ; B Curti / ; S Dakhil / ; S Denmeade / ; A Ferrari / ; T Flaig / ; N Gabrail / ; M Galsky / ; D George / ; O Goodman / ; I Gore / ; N Hahn / ; J Hainsworth / ; O Hamid / ; J Harris / ; T Hutson / ; N Iannotti / ; A Koletsky / ; P Lara / ; T Larson / ; C Logothetis / ; J May / ; J McClean / ; M Modiano / ; R Montgomery / ; L Nordquist / ; J Picus / ; C Redfern / ; M Rettig / ; S Riggs / ; P Rosen / ; C Ryan / ; M Saleh / ; J Sarantopoulos / ; A Sartor / ; H Scher / ; M Scholz / ; Z Segota / ; H Sehpande / ; N Shore / ; J Showel / ; M Smith / ; S Tagawa / ; W Tan / ; S Tejwani / ; V Tjan-Wettstein / ; P Twardowski / ; J Vacirca / ; P VanVeldhuizen / ; M Vira / ; Y Wong / ; S Wu / ; E Yu /
Comments/Corrections
Comment In:
Lancet Oncol. 2012 Oct;13(10):958-9   [PMID:  22995649 ]
Erratum In:
Lancet Oncol. 2012 Nov;13(11):e464

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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