COU-AA-302 Final Update: Abiraterone Acetate Maintains Overall Survival Advantage in Chemotherapy-Naïve Patients with Metastatic Prostate Cancer
Abiraterone acetate is a prodrug of abiraterone, a selective CYP17 inhibitor that blocks androgen synthesis, and is approved, together with prednisone, for the treatment of progressive metastatic castrate-resistant prostate cancer (mCRPC). The COU-AA-302 study was a randomized, phase 3 clinical trial of first-line abiraterone acetate therapy in patients with mCRPC and no previous chemotherapy. Two earlier planned interim analyses of this study (at 13%, 43%, and 56% of death cases) showed that abiraterone acetate plus prednisone significantly delayed disease progression and improved overall survival (OS) compared with prednisone alone, and was well tolerated (Ryan CJ, et al. N Engl J Med. 2013;368:138-148; Rathkopf DE, et al. Eur Urol. 2014;Mar 6 [Epub ahead of print]).
At ESMO 2014, Ryan and colleagues reported the prespecified final analysis of OS and safety outcomes in the COU-AA-302 trial, at 96% of planned death events (Ryan CJ, et al. ESMO 2014: Abstract 753O).
In this phase 3 clinical trial, 1088 patients with mCRPC who had not received previous chemotherapy were randomized to receive abiraterone acetate combined with prednisone or prednisone alone. The coprimary end points were radiographic progression-free survival and OS. After a median follow-up of 49.4 months, abiraterone acetate plus prednisone significantly prolonged OS compared with prednisone alone (median OS, 34.7 vs 30.3 months, respectively; P = .0027). Grade 3 or 4 adverse events that were more common in the abiraterone acetate plus prednisone arm compared with prednisone alone included hypertension (4.6% vs 3.1%), hypokalemia (2.6% vs 1.9%), and increased ALT (5.9% vs 0.7%). The incidence of fluid retention or edema was similar among the 2 arms.
Ryan and colleagues concluded that after a median follow-up of more than 4 years, abiraterone acetate with prednisone maintains its significant advantage over prednisone alone in prolonging OS, maintaining a favorable long-term safety profile, and is well tolerated.