New agents in metastatic prostate cancer.

Discoveries of molecular mechanisms and therapeutic targets in metastatic castration-resistant prostate cancer (CRPC) have led to significant advancements in the development of effective agents in this setting, with diverse mechanisms of action. Within the past 2 years, 5 agents have been approved for the treatment of patients with metastatic CRPC (cabazitaxel, abiraterone, sipuleucel-T, denosumab, and enzalutamide), and another (Alpharadin) has shown overall survival benefit in a phase III trial. This article summarizes the phase III data showing clinical benefit from these agents, highlights other promising therapies in phase III studies as single agents (PROSTVAC-VF, ipilimumab, cabozantinib), discusses important unanswered questions regarding these therapies, and provides a schema for their use based on current regulatory approval and how this is likely to evolve as data from ongoing studies are reported. Although curative interventions in metastatic CRPC still do not exist, the hope is that optimization of therapeutic strategies can reduce the morbidity and mortality associated with this disease.