Integration of immunotherapy into the management of advanced prostate cancer

Until recently, the only therapy shown to improve survival in men with metastatic castration-resistant prostate cancer (mCRPC) had been chemotherapy, usually reserved for symptomatic patients. However, sipuleucel-T, a cellular product directed toward a specific antigen, prostatic acid phosphatase, was Food and Drug Administration (FDA) approved in 2010 in the United States, based on phase 3 data showing improved overall survival in men with minimal or no symptoms due to mCRPC compared with placebo. Subsequently, several other promising immunotherapeutic approaches have advanced to study in the phase 3 setting, including ipilimumab and PROSTVAC. The demonstration of efficacy of immunotherapy in prostate cancer provides a new treatment option for men with no or few symptoms early in the course of mCRPC. Since sipuleucel-T was approved, several drugs that favorably impact survival have also been approved or are close to approval in the United States. These agents include cabazitaxel, abiraterone, radium-223, and MDV3100. There are many unresolved issues about sipuleucel-T, such as best timing in the course of mCRPC, the role for booster therapy, and the role of combinations with other active drugs, including other immune-modulating approaches. There are also many questions regarding sequencing of these new agents and, given the number of other promising agents in phase 3 trials, these questions will become more complicated, underscoring the need for better predictors of benefit for the individual patient.