ESMO 2014-ABIRATERONE FIRST LINE

A final analysis of the phase III COU-AA-302 trial showed that abiraterone acetate (Zytiga) plus prednisone significantly prolonged overall survival compared to an active control of placebo plus prednisone in men with chemotherapy-naive metastatic castration-resistant prostate cancer. The study, presented at the ESMO 2014 Congress in Madrid, demonstrated a 19% reduction in risk of death in this study population (Abstract 753O).

Phase III Trial

COU-AA-302 is an international, randomized, double-blind, placebo-controlled phase III study that included 1,088 men with metastatic castration-resistant prostate cancer who had not received prior chemotherapy. Patients were randomly assigned to receive abiraterone 1,000 mg/d administered orally plus prednisone 5 mg twice daily or placebo plus prednisone 5 mg twice daily.

The co-primary endpoints of the study were radiographic progression-free survival and overall survival. Key secondary endpoints included time to opiate use, time to initiation of chemotherapy, time to Eastern Cooperative Oncology Group (ECOG) performance status deterioration, and time to prostate-specific antigen (PSA) progression.

Long-Term Follow-up

After a median follow-up of more than 4 years (49.2 months), patients in the abiraterone arm achieved a median overall survival of 34.7 months compared with 30.3 months in the placebo arm (hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.70–0.93, P = .0033).

The final analysis is the first to demonstrate a statistically significant improvement in overall survival in this study. "Overall survival is particularly noteworthy in COU-AA-302, because 67% of men in the abiraterine-plus-prednisone arm and 80% in the control arm received subsequent therapy. This includes 44% of men in the control arm who subsequently received abiraterone plus prednisone," said lead investigator Charles Ryan, MD, Professor of Clinical Medicine, Urology at the University of California, San Francisco. "The use of subsequent therapies did not impact the statistical significance between the abiraterone and control arms—and makes these results all the more compelling after adjusting for the crossover effect."

In addition, the final analysis demonstrated a significant improvement in median time to opiate use for cancer-related pain compared to placebo plus prednisone (median, 33.4 vs. 23.4 months, respectively; HR = 0.72., 95% CI = 0.61–0.85; P = .0001). With 2 additional years of follow-up since the last clinical cutoff, the safety profile of abiraterone remained unchanged compared to previous reports.