Use of prostate-specific antigen progression (PSA-P) to predict overall survival (OS) in patients (pts) with metastatic prostate cancer (PC): Data from S9346 and S9916.

5015 Background: PSA decline has been used as an efficacy endpoint in PC trials. PSA-P is an accepted indicator of disease progression in hormone sensitive (HS) and hormone refractory (HR) PC and may play an increasing role as an endpoint. We evaluated different definitions of PSA-P as predictors of OS including Consensus Criteria (CC) (Bubley JCO '99, Scher ASCO '07) using data from two phase III trials; S9346 (HS) and S9916 ( HR) PC pts.,1,015 pts from S9346 treated with continuous androgen deprivation and 573 pts from S9916 treated with docetaxel + prednisone or mitoxantrone + prednisone had adequate PSA and follow-up data for this analysis. SWOG-DSMC approved PSA analysis from S9346 (ongoing trial). PSA-P was defined in CC '99 as an increase in PSA value of ≥ 25% and an absolute increase of ≥ 5 ng/mL over baseline or nadir; the CC'07 definition is similar except absolute PSA increase is ≥ 2 ng/mL. A time varying approach was used to analyze the association between PSA-P at any time and OS, and a landmark analysis used early PSA-P status at 7 months (ms) for S9346 or 3 ms for S9916 to predict subsequent OS. Tests for modification of this association by whether the pt had a PSA nadir on study were also performed.,In the time-varying analysis, the CC '99 and CC '07 were both strongly predictive of OS (table). Tests for interaction between PSA-P and PSA nadir were not significant for either definition. In the landmark analyses of pts on S9346 using the CC'99, median OS was 10 ms vs 43 ms in pts who did or did not have PSA-P by 7 ms; in S9916, it was 10 ms vs 18 mos for pts who did or did not have PSA-P by 3 mos.,PSA-P defined as an increase of ≥ 25% over baseline or nadir with an absolute increase of at least 2-5 ng/mL is a strong predictor of OS in metastatic HS and HR-PC irrespective of whether pts achieved a PSA nadir or not. PSA-P may be a suitable endpoint for phase II studies in these settings. [Table: see text] No significant financial relationships to disclose.