Researchers had previously demonstrated the potential validity of radiographic progression-free survival as a proxy for overall survival. For a study, they sought to investigate the validity of time to castrate-resistant disease (TCRD) and castrate-resistant free survival (CRFS) as OS surrogates in males with mHSPC and their potential application to accelerate phase 3 clinical studies. The STOPCAP M1 Collaboration looked into the supposition.
In order to compare different treatment plans for mHSPC, including androgen deprivation therapy (ADT) or ADT + docetaxel in the control or research arms, we collected individual patient data (IPD) from 13 of 26 eligible randomized trials. They assessed CRFS and TCRD as possible ICEs for OS in terms of their surrogacy. In contrast, TCRD utilized the same criteria as CRFS but only included deaths from prostate cancer. In CRFS, the criterion was time from randomization to radiographic progression, symptoms, the start of a new therapy, biochemical progression, or death from any cause, whichever occurred first. They used a two-stage meta-analytic validation methodology with patient-level and trial-level surrogacy requirements. The lowest ICE treatment impact required to estimate a non-zero effect on OS is known as the surrogate threshold effect (STE).
For a stratified study, the IPD from 8,592 patients who were randomized between 1994 and 2012 was examined. About 5,377 people passed away, and 3,971 (74%) of the fatalities were caused by prostate cancer. Patients who survived, on average, had been followed up for 6 years and 4 months. There were also 8,215 TCRD events and 8,260 CRFS events. The median OS, CRFS, and TCRD were 49.4, 13.7, and 13.3 months respectively. Both the CRFS and TTCR had STEs of 0.72.
In mHSPC patients, CRFS and TCRD do not seem to be reliable OS. surrogate endpoints.