Enzalutamide for treatment of CRPC: Rationale for sequencing and potential clinical biomarker for resistance

The androgen receptor (AR) is central to the initiation and progression of prostate cancer, even after castration. There has been some success in therapies targeting AR signaling which have been shown to extend survival in men with castration-resistant prostate cancer (CRPC). Enzalutamide is a potent AR antagonist that was initially approved in 2012 for men with CRPC who had previously failed chemotherapy treatment with docetaxel. Herein, we reviewed 2 key manuscripts that have recently appeared in the New England Journal of Medicine regarding enzalutamide. The PREVAIL Phase 3 trial was designed to evaluate enzalutamide before chemotherapy in men with CRPC. The study illustrated that 65% of patients receiving enzalutamide had radiographic-progression free survival. There was a significant risk reduction of radiographic progression or death, compared with the placebo group. The enzalutamide group's median overall survival was 32.4 months vs. 30.2 months in the placebo group.