Abiraterone for the Treatment of Metastatic Castrate-Resistant Prostate Cancer

OBJECTIVE: To review the clinical pharmacology, efficacy, and safety of abiraterone acetate for metastatic castrate-resistant prostate cancer (mCRPC) and evaluate the drug for health-system formulary inclusion. DATA SOURCES: Literature was identified through a search of MEDLINE (1977-February 2012) and International Pharmaceutical Abstracts (1977-February 2012) using the search term abiraterone. References of identified articles were reviewed. STUDY SELECTION AND DATA EXTRACTION: All clinical trials published in English were evaluated. Studies conducted in the setting of mCRPC were included in the literature review. DATA SYNTHESIS: Despite benefits from androgen deprivation for the treatment of prostate cancer, most patients experience disease progression within 12-48 months, a phase described as castrate resistant. Abiraterone is the only Food and Drug Administration approved hormonal treatment option for mCRPC in men who have received docetaxel and is recommended as a second-line agent for this indication in the National Comprehensive Cancer Network prostate cancer guidelines. One Phase 3 study, 2 Phase 2 studies, and 2 Phase 1 studies conducted in the setting of second-line treatment of mCRPC were identified. Treatment with abiraterone was associated with at least a 50% reduction in prostate-specific antigen (PSA) in 38-51% of patients; PSA progression ranged from 5.6-10.2 months. The only study assessing mortality outcomes found a 13% absolute reduction in mortality (ie, 42% vs 55%; HR 0.65; 95% CI 0.54 to 0.77), relative to placebo, over a median 12.8 months of follow-up. Abiraterone has been compared only to placebo, not to existing treatment options. CONCLUSIONS: Abiraterone provides a moderate improvement in disease progression and mortality in a patient population with limited treatment options. It is recommended to add this medication to outpatient formularies restricted to second-line treatment of mCRPC.