Abiraterone for Castration-Resistant Metastatic Prostate Cancer

For the past 7 decades, the initial management of metastatic prostate cancer focused on suppressing testosterone by a variety of means, such as with surgery (bilateral orchiectomy) or medical treatment (estrogens and, later, luteinizing-hormone–releasing hormone [LHRH] agonists). The typical natural history resulted in disease control for 12 to 36 months, with disease progression typically referred to as “hormone refractory” or “androgen independent.” Recent progress in understanding the disease biology provided ample evidence of the benefit of targeting the androgen receptor. But, until recently, therapy options to take advantage of this knowledge were lacking.

Now, investigators have conducted an industry-funded, phase III, multinational, randomized, controlled trial of abiraterone (Zytiga) — a selective, androgen biosynthesis inhibitor that blocks cytochrome P450 c17 (a critical enzyme in testosterone synthesis), thereby impeding androgen production in the testes, adrenal glands, and prostate tumors. A total of 1100 men with castration-resistant metastatic prostate cancer (CRMPC) previously treated with docetaxel-based chemotherapy were randomly assigned in a 2:1 ratio to receive daily abiraterone (1000 mg) plus prednisone (10 mg) or placebo plus prednisone. Patients could have received up to two separate cytotoxic regimens. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) and prostate-specific antigen (PSA) response.

After median follow-up of 12.8 months, OS was superior among patients who received abiraterone versus placebo (14.8 vs. 10.9 months; hazard ratio, 0.65), as were median PFS (5.6 vs. 3.6 months) and PSA response rate (29% vs. 6%; P<0.001 for all). Therapy was generally well tolerated; mineralocorticoid-related adverse events (fluid retention, hypertension, hypokalemia) were more common in the abiraterone group than in the placebo group.