Published online Jun 26, 2014. doi: 10.5662/wjm.v4.i2.123
Revised: January 19, 2014
Accepted: March 17, 2014
Published online: June 26, 2014
Processing time: 279 Days and 4 Hours
AIM: To review the definition and performance of the commonly used end points in trials of systemic therapies in metastatic castration-resistant prostate cancer patients.
METHODS: A literature search was undertaken on PubMed database to identify studies meeting established criteria, with the aim of selecting randomized clinical trials and study definition and performance of their end points. The end points were grouped into three categories: overall survival (OS), time-to-event end points, and response end points. A special analysis was performed for secondary end points of the studies which documented a benefit in OS in the experimental arm. Finally, publishes analyses for surrogacy of the included end points were also reported.
RESULTS: OS, time-to-event and response end points in 31 selected trials were analyzed. OS was the primary end point in 14 trials, and the secondary end point in 17. A time-to-event end point was the primary end point in 8 studies, and the secondary end point in 22; the most reported time-to-event end points were composite end points, and the events changed among trials. A response end point was the primary end point in 9 studies, in 3 it was prostate-specific antigen (PSA)-related, in 3 pain-related and in 3 mixed. A response end point was the secondary end point in 19 studies: PSA response and radiologic response were the most frequently used secondary end points in 19 and 11 trials, respectively, while pain response was used in 5 studies.
CONCLUSION: A homogeneous definition of progression in future trials is mandatory. Among response end points, pain-response and PSA-response appear to be the most reliable.
Core tip: The approval in the last decade of new drugs that have increased survival of patients with metastatic castration-resistant prostate cancer (mCRPC) has weakened the role of overall survival (OS) as end point. The prevailing bone-only spread of mCRPC severely limits disease evaluation using the standard criteria of conventional radiology. On the other hand, recent retrospective analyses of prostate-specific antigen response after chemotherapy did not support this measure as a surrogate end point of OS. This lack of reliable surrogate end points is a problem for the conduction of phase II studies which test the activity of new drugs.