Prognostic Association of Prostate-specific Antigen Decline with Clinical Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Treated with Enzalutamide in a Randomized Clinical Trial.

Background: In the PREVAIL study, enzalutamide provided significant improvements versus placebo in clinical outcomes in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (mCRPC). The association of post-treatment prostate-specific antigen (PSA) decline with clinical outcomes may provide important prognostic information.

Objective: To evaluate associations between the magnitude of PSA decline from baseline to month 3 and clinical outcomes among enzalutamide recipients.

Design, Setting, And Participants: This was a post hoc retrospective analysis of PREVAIL, an international, randomized, double-blind, placebo-controlled phase 3 study. Men with mCRPC and no prior chemotherapy from the enzalutamide arm were included (n=872). Patients were grouped by confirmed maximal PSA decline from baseline to month 3 of treatment (n=795 evaluable).

Outcome Measurements And Statistical Analysis: Primary outcomes were overall survival and radiographic progression-free survival. Secondary outcomes included PSA progression-free survival, radiographic response, and degradation of Functional Assessment of Cancer Therapy-Prostate score, which were estimated using the Kaplan-Meier method.

Results And Limitations: Following 3mo of enzalutamide treatment, 88% (701/795), 80% (639/795), and 39% (307/795) of patients had postbaseline confirmed maximal PSA declines of ≥30%, ≥50%, and ≥90%, respectively, whereas 12% (94/795) had no confirmed maximal PSA decline or a decline of <30%. Greater degrees of PSA decline within the first 3mo of enzalutamide treatment were increasingly associated with longer overall survival, time to PSA and radiographic progression, higher objective soft-tissue responses, and longer time to quality-of-life deterioration than no PSA decline or declines of <30% from baseline. PSA flares (rise followed by fall) after enzalutamide treatment were rare (<1%).

Conclusions: The magnitude of PSA decline after 3mo of enzalutamide therapy was strongly associated with better clinical and patient-reported outcomes. This updated prognostic information is of clinical value to this patient population and their health care providers.

Patient Summary: We report that decreases in PSA levels are closely linked to better health and survival after 3mo of enzalutamide treatment in men with metastatic prostate cancer. The PREVAIL trial is registered at clinicaltrials.gov as NCT01212991.