Development of enzalutamide for metastatic castration-resistant prostate cancer.

Prostate cancer is the most prevalent cancer among men in the Western world and a leading cause of cancer-related death among men. Within 5 years of initial diagnosis, approximately 10–20% of men will progress to metastatic castration-resistant prostate cancer (mCRPC). Often characterized by increased prostate-specific antigen and androgen receptor (AR) activity despite castrate levels of testosterone, mCRPC has a poor prognosis and causes significant deterioration in quality of life. Enzalutamide is an AR inhibitor approved to treat mCRPC in both post- and pre-chemotherapy settings on the basis of results from two phase III randomized, placebo-controlled trials, AFFIRM and PREVAIL, respectively. Enzalutamide significantly prolonged overall survival (hazard ratio (HR), AFFIRM 0.63, 95% confidence interval (CI) 0.53–0.75, P < 0.001; PREVAIL 0.71, 95% CI 0.60–0.84, P < 0.001) and radiographic progression (HR, AFFIRM 0.40, 95% CI 0.35–0.47, P < 0.001; PREVAIL 0.19, 95% CI 0.15–0.23, P < 0.001), and significantly improved quality of life. With an acceptable safety profile, enzalutamide is one of several emerging alternative options for men with mCRPC. Studies are ongoing to explore potential benefits of enzalutamide in earlier stages of prostate cancer and in breast cancer.