Abiraterone acetate significantly prolongs survival in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer

Data from the phase III COU-AA-302 study show that abiraterone acetate (AA) significantly prolongs the overall survival (OS) of patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Moreover, AA was shown to delay the need for opiate analgetics of these patients.

AA is a prodrug of abiraterone, a selective CYP17 inhibitor that blocks androgen biosynthesis and is approved in combination with prednisone, for the treatment of patients with progressive mCRPC. Planned interim analyses of COU-AA-302 (at 13%, 43%, and 56% death events) in mCRPC chemotherapy-naïve patients previously showed that AA + prednisone significantly delayed disease progression and improved OS compared with prednisone alone and was well tolerated. During ESMO 2014, the pre-specified final analysis (96% of planned death events) of the OS and safety outcomes were presented.

In COU-AA-302, a total of 1,088 patients with progressive mCRPC, who did not receive prior chemotherapy, was randomized 1:1 to receive AA + prednisone or prednisone alone. The co-primary endpoints of this phase III study were radiographic progression-free survival (rPFS) and OS. With median follow-up of 49.2 months, AA + prednisone significantly prolonged rPFS compared to prednisone alone (16.5 vs. 8.2 months; HR[95%CI]: 0.52[0.45-0.61]; p< 0.0001). Also, the OS was significantly longer with AA plus prednisone compared with prednisone alone (median OS: 34.7 vs. 30.3 months; HR[95%CI]: 0.81 [0.70-0.93]; p = 0.0033). Of note, the AA treatment effect was even more pronounced when adjusting for the 44% of patients in the prednisone alone arm who received subsequent AA (HR: 0.74). This OS advantage in favor of AA plus prednisone was observed across all patient subgroups. Furthermore, AA plus prednisone was also associated with a significant improvement in the time to opiate use for cancer-related pain (33.4 months with AA plus prednisone vs. 23.4 months with prednisone alone; HR[95%CI]: 0.72 [0.61-0.85]; p< 0.0001).

Adverse events (grade 3/4) of special interest which were more common with AA + prednisone vs. prednisone alone were hypertension (4.6% vs. 3.1%); hypokalemia (2.6% vs. 1.9%); ALT increase (5.9% vs. 0.7%); AST increase (3.3% vs. 0.9%) and fluid retention/edema (1.1% vs. 1.7%).

In summary, the COU-AA-302 pre-specified, final analysis demonstrates a statistically significant OS benefit with AA + prednisone even though a large number of patients in the prednisone arm received AA + prednisone and other subsequent therapy. With nearly an additional 2 years of follow-up since last reported, the combination of AA + prednisone maintains a favorable safety profile and is well tolerated.


Ryan C, Smith M, Fizazi K et al. Final overall survival (OS) analysis of COU-AA-302, a randomized phase 3 study of abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) without prior chemotherapy. Presented at ESMO 2014; Abstract 753O.

Speaker Charles Ryan


Prof. Charles Ryan, MD, PhD,
Associate Clinical Professor, Department of Medicine (Hematology/Oncology), UCSF, San Francisco, USA


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