Final Survival Analysis in COU-AA-302 Shows Benefit of Adding Abiraterone to Prednisone in Chemotherapy-Naive Castration-Resistant Prostate Cancer


Key Points

  • The addition of abiraterone to prednisone significantly prolonged overall survival.
  • The abiraterone group had significantly prolonged time to opiate use.

In the final analysis of overall survival in the COU-AA-302 trial, reported in The Lancet Oncology by Ryan et al, the addition of abiraterone acetate (Zytiga) to prednisone significantly prolonged survival in chemotherapy-naive patients with castration-resistant prostate cancer. Abiraterone had been approved for use in this setting on the basis of improved radiographic progression-free survival in COU-AA-302.

Study Details

In this double-blind trial, 1,088 asymptomatic or mildly symptomatic patients were randomly assigned between April 2009 and June 2010 to receive abiraterone at 1,000 mg once daily plus prednisone at 5 mg twice daily (n = 546) or prednisone plus placebo (n = 542). The coprimary endpoints were radiographic progression-free survival and overall survival.

Improved Overall Survival

The difference in overall survival for abiraterone-prednisone vs placebo-prednisone failed to cross the prespecified efficacy boundary in the first (13% of expected events; hazard ratio [HR] = 1.08, P = .69), second (43% of expected events; HR = 0.75, P = .0097), and third interim analyses (56% of expected events; HR = 0.79, P = .015).

At a median follow-up of 49.2 months, after 96% of expected events, median overall survival was 34.7 months in the abiraterone group vs 30.3 months in the control group (HR = 0.81, P = .0033) on final analysis. The effect of abiraterone was consistent across all prespecified subgroups. The benefit remained significant in analysis (iterative parameter estimate method) adjusting for crossover to abiraterone (HR = 0.74, 95% confidence interval = 0.60–0.88) and in multivariate analysis adjusting for baseline prognostic factors (HR = 0.79, P = .0013).

Subsequent Treatments

Overall, 238 patients (44%) in the placebo group subsequently received abiraterone plus prednisone, including 93 who crossed over on the basis of a study protocol amendment. Abiraterone was also received by 13% of the abiraterone group after progression. A total of 67% of the abiraterone group and 80% of the placebo group received subsequent therapy, with the most common treatments in addition to abiraterone consisting of docetaxel (57% and 61%), cabazitaxel (18% and 19%), and enzalutamide (16% and 10%).

As was also found in interim analysis, median time to opiate use for cancer-related pain was significantly prolonged in the abiraterone group (33.4 vs 23.4 months, HR = 0.72, P < .0001).

Adverse Events

Adverse event data were similar to data reported from interim analysis. Adverse events led to discontinuation of treatment in 9% of the abiraterone group and 6% of the placebo group (7% and 4% considered treatment-related). The most common grade 3 or 4 adverse events of special interest were cardiac disorders (8% vs 4%), increased ALT (6% vs < 1%), and hypertension (5% vs 3%). No treatment-related deaths were observed.

The investigators concluded: “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.”

Charles J. Ryan, MD, of University of California San Francisco Helen Diller Family Comprehensive Cancer Center, is the corresponding author for the Lancet Oncology article.

The study was funded by Janssen Research & Development. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.