Emerging therapies in metastatic castration-sensitive and castration-resistant prostate cancer

PURPOSE OF REVIEW: Therapeutic options for men with metastatic prostate cancer are expanding. Here we discuss the scientific progress in this disease that led to approval of several agents in the last decade and highlight ongoing clinical investigation. RECENT FINDINGS: In androgen-sensitive disease, trials are evaluating the role of intermittent androgen-deprivation therapy, early chemotherapy, and novel targeted and hormonal therapies. For chemotherapy-naive, metastatic castration-resistant prostate cancer (mCRPC), abiraterone is effective. Trials with additional agents targeting androgen receptor (AR) signaling, such as TAK-700 and enzalutamide, are ongoing. Other agents in development target the endothelin pathway, angiogenesis, AR chaperones, and immune mechanisms. Docetaxel with prednisone remains the standard first-line chemotherapeutic regimen as trials incorporating novel agents with docetaxel have been negative. Postdocetaxel, enzalutamide improves survival. Early results with cabozantinib are encouraging, and phase III studies are ongoing. Denosumab and radium-223 reduce the risk of skeletal-related events (SREs), but only radium-223 improves survival. SUMMARY: Progress in understanding the disease biology and mechanisms of castration resistance led to significant therapeutic advancements, particularly in the setting of mCRPC in which several phase III trials, each incorporating agents with different mechanisms of action, have improved survival. As a result, new options exist, and the standard of care has changed significantly. Further advances are anticipated.