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.

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.

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

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).

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.

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%).

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.

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.

European urology oncology. 2018 Dec 03 [Epub ahead of print]

Andrew J Armstrong, Ping Lin, Celestia S Higano, Peter Iversen, Cora N Sternberg, Bertrand Tombal, De Phung, Teresa Parli, Andrew Krivoshik, Tomasz M Beer

Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA. Electronic address: ., Pfizer Inc., San Francisco, CA, USA., University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Weill Cornell Medical Center, New York, NY, USA., Cliniques universitaires Saint-Luc, Brussels, Belgium., Astellas Pharma Europe B.V., Leiden, The Netherlands., Astellas Pharma Inc., Northbrook, IL, USA., OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.

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