MedicalResearch.com: What are the main findings of the study?
Dr. Halabi: The purpose of assessing surrogate endpoints is to allow for a more rapid and efficient determination of whether a given therapy provides clinical benefit to patients by prolonging their life.
We sought to evaluate PSA kinetics as surrogate endpoints for overall survival (OS) in mCRPC patients who were receiving second line chemotherapy (cabazitaxel or mitoxantrone) following progression after docetaxel. Using different analytical approaches, we found that PSA declines within the first three months of treatment are not appropriate as surrogate markers of clinical benefit in men who were receiving second line chemotherapy.
This analysis has important clinical care and study design implications: it has become common to use ≥30% decline in PSA as a clinical trial endpoint for all patients with metastatic CRPC, based on the original front-line docetaxel data. The data presented in this study suggest that this is erroneous. Further we believe these data are important because they demonstrate that there are different disease states within the group of patients with “metastatic CRPC”. To make the assumption that the same surrogate endpoint can be used across the board may seem like an obvious mistake, but permeates the literature.
MedicalResearch.com: Were any of the findings unexpected?
Dr. Halabi: The results were not unexpected as a greater than or equal than 30% decline in PSA fulfilled the Prentice’s criteria in the TAX327 trial, but found only a modest surrogate effect for survival benefit in mCRPC chemotherapy-naïve men who received docetaxel.
MedicalResearch.com :What should clinicians and patients take away from your report?
Dr. Halabi: PSA alone should not be used to guide treatment, in other words, decisions to stop treatment should not be based by short term isolated changes in PSA.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Halabi: There is a great need to find appropriate surrogate endpoints of overall survival. Future analysis will need to be performed with new drugs and new therapies to make sure that these results hold.