ORLANDO—Enzalutamide significantly improves overall and radiographic progression-free survival among men with metastatic castration-resistant prostate cancer (mCRPC) not previously treated with chemotherapy, according to data presented at the American Urological Association 2014 annual meeting. Researchers observed these benefits in men with and without visceral disease.
The double-blind, randomized PREVAIL study, led by Christopher Evans, MD, professor of urology at the University of California Davis, included 1,717 men with mCRPC, a group that included 1,513 patients (88.1%) without and 204 (11.9%) with visceral disease at screening (63.7% lung and 36.3% liver and/or lung).
Compared with men who received placebo, those treated with enzalutamide had an 81% and 29% reduction in the relative risk of radiographic disease progression and all-cause mortality, respectively, Dr. Evans reported. They also had a 65% reduction in the relative risk of starting cytotoxic chemotherapy.
Based on statistically significant benefits for enzalutamide in radiographic progression-free and overall survival, the study’s Data Monitoring Committee recommended that the study be stopped at the interim analysis. Dr. Evans noted that an important aspect of the trial was the inclusion of chemotherapy-naïve mCRPC patients with visceral disease.
The FDA approved enzalutamide on August 31, 2012 for the treatment of patients with mCPRC who have previously received docetaxel. The agency based the approval a single randomized, placebo-controlled, multicenter trial enrolling 1,199 patients who were randomly assigned to receive enzalutamide 160 mg orally once daily (800 patients) or placebo (399 patients).
Study treatment continued until disease progression, initiation of new systemic antineoplastic treatment, unacceptable toxicity, or withdrawal.
Overall survival was the primary efficacy endpoint. At a pre-specified interim analysis, the median overall survival was 18.4 months in the enzalutamide compared with 13.6 months in the placebo arm, a difference that translated into a significant 37% decreased risk of death.
Enzalutamide is sold under the brand name Xtandi by Medivation, Inc., and Astellas Pharma US, Inc.