Clinical endpoints for drug development in prostate cancer

Overall survival remains the benchmark in phase III settings of novel agents in castration-resistant metastatic prostate cancer. This review highlights many of the current potential early measures of response and clinical benefit that are worthy of future study and validation in this disease.

The clinical evaluation of novel agents in advanced prostate cancer remains challenging for several reasons. Men with metastatic prostate cancer often have bone-only disease in which formal radiologic response and progression criteria may not apply. Declines in serum prostate-specific antigen levels may be modest surrogates of response to cytotoxic agents such as docetaxel, but have not been validated for agents with novel mechanisms of action, such as antiangiogenic, immunologic, or cytostatic drugs. Novel radiologic imaging techniques such as PET scans are not yet validated for use in monitoring or staging advanced prostate cancer. Measures of delay, control, and palliation of metastatic disease such as pain response, time to progression and progression-free survival, while appealing endpoints that may highlight the clinical benefit of novel agents, have been difficult to define rigorously and have not yet demonstrated adequate surrogacy for overall survival.

The measures of response highlighted in this review, if validated, may improve the current evaluation of novel agents in phase II settings and the potential accelerated approval of these agents.