ArticlesAbiraterone 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
Introduction
An overarching feature of the recent management of metastatic castration-resistant prostate cancer is the use of sequential therapies. Before 2010, the only approved systemic treatment associated with improved overall survival was docetaxel.1, 2 Over the past 4 years, five therapeutics with demonstrated survival benefit in randomised clinical studies have become available, and are commonly used in sequence.3, 4, 5, 6, 7, 8, 9, 10, 11 Given the chronicity and heterogeneity of metastatic castration-resistant prostate cancer, administration of such subsequent therapies may confound the measurement of the effect of a particular treatment on overall survival.
Abiraterone acetate is a prodrug of abiraterone, an orally available inhibitor of the cytochrome P450 c17 enzyme complex critical to androgen production. Oral abiraterone acetate plus prednisone demonstrated a significant improvement in survival, compared with placebo plus prednisone, for patients with metastatic castration-resistant prostate cancer with progression of disease after administration of chemotherapy.5, 6 In chemotherapy-naive patients, abiraterone acetate plus prednisone delayed radiographic progression, prevented the onset of symptoms, and preserved quality of life, compared with placebo plus prednisone.9, 10, 12 However, at the interim analyses, overall survival results did not cross the prespecified efficacy boundary for statistical significance as defined by O'Brien and Fleming.13
Here, we present the final overall survival analysis of the COU-AA-302 trial of abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer.
Section snippets
Study design and participants
The patient population for this multinational, double-blind, randomised, placebo-controlled phase 3 trial has been described previously.9, 10 Briefly, patients aged 18 years or over with histologically or cytologically confirmed adenocarcinoma of the prostate, prostate-specific antigen (PSA) progression according to Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria, or radiographic progression in soft tissue or bone with or without PSA progression, ongoing androgen deprivation
Results
1088 patients were randomly assigned to receive study treatment between April 28, 2009, and June 23, 2010 (figure 1); treatment groups were well balanced.9, 10 The clinical cutoff date for the preplanned final analysis was March 31, 2014. At the time of the final analysis, treatment was ongoing for 42 (8%) patients in the abiraterone acetate group and for no patients in the placebo group. At the final analysis, 238 (44%) patients from the placebo group had subsequently received abiraterone
Discussion
In this final analysis of the COU-AA-302 phase 3 trial, overall survival for men with chemotherapy-naive metastatic castration-resistant prostate cancer was significantly longer with abiraterone acetate and prednisone than with placebo and prednisone, meeting the protocol-specified criterion for statistical significance. Thus both coprimary endpoints—radiographic progression-free survival and overall survival—have been shown to be significantly improved by the addition of abiraterone acetate to
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