Prognostic associations of prostate-specific antigen (PSA) decline with survival, radiographic response and progression in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide

Abstract

Background: In the PREVAIL clinical trial, enzalutamide provided significant improvements vs placebo in radiographic progression-free survival (rPFS) and overall survival (OS) in chemotherapy-naïve men with mCRPC. This post hoc analysis aimed to evaluate the prognostic association between the magnitude of PSA decline from baseline and clinical outcomes in PREVAIL. Methods: Men from the enzalutamide and placebo arms of PREVAIL were grouped into categories of confirmed maximal PSA decline from baseline at month 3 of treatment: no decline/decline <30% and≥ 30%, ≥50% or≥90% decline. Confirmation required PSA decline on≥1 consecutive visit after month 3. Best overall soft-tissue response (per RECIST v1.1) was determined for patients with measurable disease at baseline (data cutoff: 16 Sep 2013). Time to PSA progression (data cutoff: 16 Sep 2013), rPFS (per PCWG2; data cutoff: 6 May 2012) and OS (data cutoff: 16 Sep 2013) were estimated using the Kaplan-Meier method. Results: In PREVAIL, men were randomized to enzalutamide (n=872) or placebo (n=845). Most men in the placebo arm (66%, 558/845) had no PSA decline/decline <30%, in contrast to 11% (94/872) in the enzalutamide arm. In the enzalutamide arm, 81% (701/872) of men had a PSA decline of≥30% from baseline at week 13, 73% (639/ 872) had a PSA decline of≥50% and 35% (307/872) had a PSA decline of≥90%. Key outcomes for the enzalutamide arm are provided by PSA decline category in the Table. PSA flare (rise followed by a fall) after 3 months was rare with enzalutamide (< 1%). Conclusions: PSA declines after 3months of enzalutamide therapy are strongly associated with soft-tissue response and improvements in rPFS and OS. Providing updated prognostic information to chemotherapy-naïve men with mCRPC can be of clinical value given the heterogeneity of long-term outcomes. (Table presented).