Novel and bone-targeted agents for CRPC

Clearly, no neoplasm other than prostate cancer has benefited from so many breakthroughs since the beginning of this decade: the past two years can be considered exceptional due to the number of emerging agents against castration-resistant prostate cancer (CRPC), which have demonstrated positive outcomes in phase III trials. Until 2010, docetaxel (Taxotere) was the only agent capable of improving survival in patients with metastatic CRPC. Since then, positive results from phase III trials have been reported for sipuleucel-T, cabazitaxel, denosumab, abiraterone, radium-223, and enzalutamide, while other promising agents including notably orteronel, ipilimumab and cabozantinib are currently under study. Taken together, the incorporation of these agents in the routine management of patients with CRPC is likely to expand their median life expectancy, which was only ~1 year until the early 2000, to >30 months in the near future. The availability of these agents will lead to new challenges and questions, such as: Can our societies afford the costs? Should we use these agents sequentially or in combination with an incremental benefit? Can we personalise treatment based on the biology of the individual's disease? How will we develop new active compounds in the context where a half dozen approved agents may confound their potential overall survival effect?