WASHINGTON, DC USA (UroToday.com) - An update of COU-AA-301 by Dr. Fred Saad confirms the oncologic benefits and safety profile of Abiraterone acetate (AA) in patients with metastatic castration-resistant prostate cancer (mCRPC) post-docetaxel chemotherapy.
AA is a selective androgen biosynthesis inhibitor that blocks the action of CYP17 and inhibits persistent androgen synthesis from adrenal and intratumoral sources. This mechanism is relevant since CRPCs remain dependent on androgen receptor (AR) signaling. These investigators have previously reported that AA + prednisone (P) improves overall survival in mCRPC progressing after docetaxel. The FDA has recently approved AA + P for this indication. This presentation is an updated safety outcomes and radiographic and PSA response data from this study. In COU-AA-301 (NCT00638690), pts with docetaxel-treated mCRPC were randomized 2:1 to AA (1000 mg) + P (5 mg BID) (n=797) or placebo + P (n=398) at 147 centers in 13 countries. Safety assessments were standard; the primary endpoint was overall survival (OS). PSA and radiographic assessments were adapted from the PCWG2 criteria.
A total of 1,195 patients were enrolled. Based on a pre-specified interim analysis, the IDMC recommended that the study be unblinded. Grade 3/4 adverse events occurred in 55% of pts with AA vs. 58% with placebo. Frequently occurring (> 5%) adverse events with AA compared with placebo were: fatigue (8% vs. 10%), anemia (7.5% vs. 7.4%), back pain (6% vs. 10%), and spinal cord compression (3% vs. 5%); the most common grade 3/4 adverse events were decreased lymphocytes (21% vs. 23%) and increased ALP (18% vs. 13%). Grade 3/4 adverse events of special interest (AA vs. placebo) were: fluid retention (2.3% vs. 1%), hypokalemia (3.8% vs. 0.8%), LFT abnormalities (3.5% vs. 3.0%), hypertension (1.3% vs. 0.3%), and cardiac disorders (4.1% vs. 2.3%). They concluded that these data confirm the oncologic benefits of AA + P with a good safety profile.
Presented by Fred Saad, et al. at the American Urological Association (AUA) Annual Meeting - May 14 - 19, 2011 - Walter E. Washington Convention Center, Washington, DC USA
Reported for UroToday by Christopher P. Evans, MD, FACS, Professor and Chairman, Department of Urology, University of California, Davis, School of Medicine.