PFS Endpoints May Be OS Surrogates for Metastatic HSPC

Radiographic progression-free survival and clinical progression-free survival appear to be valid surrogate endpoints for overall survival in studies of men with metastatic-hormone sensitive prostate cancer (mHSPC), according to results presented at the 2022 ASCO Annual Meeting (Abstract 5006).

Susan Halabi, PhD, of Duke University Medical Center, and colleagues used individual patient data from 13 out of 26 eligible randomized trials that compared treatment regimens in mHSPC. The trials included 8,592 patients on studies from 1994 to 2012.

According to the abstract, Halabi and colleagues hypothesized that radiographic progression-free survival and clinical progression-free survival are valid surrogates for overall survival in this patient population. If so, these endpoints could be used to expediate phase-3 clinical trials.

Radiographic progression-free survival was defined as time from randomization to radiographic progression or death from any cause. Clinical progression-free survival was defined as time from randomization to date of radiographic progression, symptoms, initiation of new treatment, or death.

The researchers implemented a two-stage meta-analytic validation model where conditions of trial level and patient level surrogacy had to be met. They then computed the surrogate threshold effect (STE), which is the minimum ICE treatment effect necessary to estimate a non-zero effect on overall survival.

There were 5,377 deaths among patients in these trials, of which the majority (74%) were due to prostate cancer. Median follow-up for surviving patients was 75.6 months.

The median overall survival was 49.4 months. Median radiographic and clinical progression-free survival were 26.8 and 25.2, respectively. The STE was 0.82 for radiographic progression-free survival and 0.84 for clinical progression-free survival.

According to the researchers, “a surrogate threshold effect of 0.82 or higher makes it viable for either radiographic progression-free survival of clinical progression-free survival to be used as the primary endpoint as a surrogate for overall survival in phase-3 mHSPC trials.”