Abiraterone for the treatment of metastatic castrate-resistant prostate cancer

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.

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.

All clinical trials published in English were evaluated. Studies conducted in the setting of mCRPC were included in the literature review.

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.

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.