Abiraterone acetate significantly prolonged overall survival in patients with castration-resistant metastatic prostate cancer that progressed on docetaxel-based chemotherapy. The favorable effect of abiraterone was consistent across all prespecified subgroups, with a similar survival benefit as in the total population. These interim results of the international, multicenter, phase III COU-AA-301 trial led to stopping the study after improved survival was demonstrated, and placebo patients were then switched to abiraterone. The interim analysis was protocol-specified.

"Abiraterone is a new treatment option that prolongs survival in men with castration-resistant prostate cancers that have been previously treated with chemotherapy. Considering castration-resistant prostate cancer as hormone refractory may deny these patients safe and effective treatment," said lead author Howard Scher, MD, Chief of the Genitourinary Oncology Service at Memorial Sloan-Kettering Cancer Center.

Abiraterone is a selective androgen biosynthesis inhibitor that blocks the action of CYP17. Preclinical evidence shows that abiraterone blocks androgen synthesis from adrenal and intratumoral sources, suppressing an important stimulus for growth of metastatic castration-resistant disease.

Study Design and Results

The study included 1,200 patients with castration-resistant metastatic prostate cancer for whom one or two previous lines of chemotherapy (at least one with docetaxel) had failed. Patients were randomly assigned to abiraterone plus prednisone vs placebo plus prednisone. The two arms were well balanced for demographic and disease characteristics.

Abiraterone achieved significantly superior overall survival vs placebo: a median of 14.8 months vs 10.9 months, representing a 35% relative risk reduction of mortality (P < .0001).  The survival benefit was consistent across subgroups in a preplanned analysis stratified for number of lines of prior chemotherapy, performance status, pain scores, and radiographic progression-free survival. Total and confirmed prostate-specific antigen response rates were also superior in the abiraterone-treated arm (see Table 1).

Adverse events of all grades and of grades 3 and 4 were similar between the two treatment arms. The most frequent adverse events (of all grades) in the abiraterone-treated patients were fluid retention (31%), hypokalemia (17%), hypertension (10%), cardiac disease (13%), and liver function test abnormalities (10%).

"These side effects were manageable and consistent with the known hormonal effects of the drug," Dr. Scher stated. ■

Financial Disclosure: Dr. Scher disclosed a relationship with Cougar Biotechnology, a subsidiary of Johnson & Johnson, but reported that he does not receive direct compensation. In addition, Cougar Biotechnology funded the study through an institutional clinical research agreement with MSKCC. Dr. Scher holds stock with Johnson & Johnson.

Reference

1. Scher HI, Logothetis C, Molina A, et al: Improved survival outcomes in clinically relevant patient subgroups from COU-AA-301, a phase III study of abiraterone acetate (AA) plus prednisone (P) in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel-based chemotherapy. Genitourinary Cancers Symposium. Abstract 4. Presented February 17, 2011.