Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study - 30/01/15
, Matthew R Smith, ProfMD b, Karim Fizazi, ProfMD c, Fred Saad, ProfMD d, Peter F A Mulders, ProfMD e, Cora N Sternberg, MD f, Kurt Miller, ProfMD g, Christopher J Logothetis, ProfMD h, Neal D Shore, MD i, Eric J Small, ProfMD a, Joan Carles, MD j, Thomas W Flaig, MD k, Mary-Ellen Taplin, MD l, Celestia S Higano, ProfMD m, Paul de Souza, ProfMB n, Johann S de Bono, ProfMB ChB o, Thomas W Griffin, MD p, Peter De Porre, MD q, Margaret K Yu, MD p, Youn C Park, PhD r, Jinhui Li, PhD r, Thian Kheoh, PhD p, Vahid Naini, PharmD p, Arturo Molina, MD s, Dana E Rathkopf, MD tfor the COU-AA-302 Investigators†
Summary |
Background |
Abiraterone acetate plus prednisone significantly improved radiographic progression-free survival compared with placebo plus prednisone in men with chemotherapy-naive castration-resistant prostate cancer at the interim analyses of the COU-AA-302 trial. Here, we present the prespecified final analysis of the trial, assessing the effect of abiraterone acetate plus prednisone on overall survival, time to opiate use, and use of other subsequent therapies.
Methods |
In this placebo-controlled, double-blind, randomised phase 3 study, 1088 asymptomatic or mildly symptomatic patients with chemotherapy-naive prostate cancer stratified by Eastern Cooperative Oncology performance status (0 vs 1) were randomly assigned with a permuted block allocation scheme via a web response system in a 1:1 ratio to receive either abiraterone acetate (1000 mg once daily) plus prednisone (5 mg twice daily; abiraterone acetate group) or placebo plus prednisone (placebo group). Coprimary endpoints were radiographic progression-free survival and overall survival analysed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT00887198.
Findings |
At a median follow-up of 49·2 months (IQR 47·0–51·8), 741 (96%) of the prespecified 773 death events for the final analysis had been observed: 354 (65%) of 546 patients in the abiraterone acetate group and 387 (71%) of 542 in the placebo group. 238 (44%) patients initially receiving prednisone alone subsequently received abiraterone acetate plus prednisone as crossover per protocol (93 patients) or as subsequent therapy (145 patients). Overall, 365 (67%) patients in the abiraterone acetate group and 435 (80%) in the placebo group received subsequent treatment with one or more approved agents. Median overall survival was significantly longer in the abiraterone acetate group than in the placebo group (34·7 months [95% CI 32·7–36·8] vs 30·3 months [28·7–33·3]; hazard ratio 0·81 [95% CI 0·70–0·93]; p=0·0033). The most common grade 3–4 adverse events of special interest were cardiac disorders (41 [8%] of 542 patients in the abiraterone acetate group vs 20 [4%] of 540 patients in the placebo group), increased alanine aminotransferase (32 [6%] vs four [<1%]), and hypertension (25 [5%] vs 17 [3%]).
Interpretation |
In this randomised phase 3 trial with a median follow-up of more than 4 years, treatment with abiraterone acetate prolonged overall survival compared with prednisone alone by a margin that was both clinically and statistically significant. These results further support the favourable safety profile of abiraterone acetate in patients with chemotherapy-naive metastatic castration-resistant prostate cancer.
Funding |
Janssen Research & Development.
Le texte complet de cet article est disponible en PDF.Plan
Vol 16 - N° 2
P. 152-160 - février 2015 Retour au numéro
Article précédent
- Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials
- James Chih-Hsin Yang, Yi-Long Wu, Martin Schuler, Martin Sebastian, Sanjay Popat, Nobuyuki Yamamoto, Caicun Zhou, Cheng-Ping Hu, Kenneth O’Byrne, Jifeng Feng, Shun Lu, Yunchao Huang, Sarayut L Geater, Kye Young Lee, Chun-Ming Tsai, Vera Gorbunova, Vera Hirsh, Jaafar Bennouna, Sergey Orlov, Tony Mok, Michael Boyer, Wu-Chou Su, Ki Hyeong Lee, Terufumi Kato, Dan Massey, Mehdi Shahidi, Victoria Zazulina, Lecia V Sequist
- Disease-free survival after complete mesocolic excision compared with conventional colon cancer surgery: a retrospective, population-based study
- Claus Anders Bertelsen, Anders Ulrich Neuenschwander, Jens Erik Jansen, Michael Wilhelmsen, Anders Kirkegaard-Klitbo, Jutaka Reilin Tenma, Birgitte Bols, Peter Ingeholm, Leif Ahrenst Rasmussen, Lars Vedel Jepsen, Else Refsgaard Iversen, Bent Kristensen, Ismail Gögenur, on the behalf of the Danish Colorectal Cancer Group
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?