Primary, secondary, and quality-of-life endpoint results from PREVAIL, a phase 3 study of enzalutamide in men with metastatic castration resistant prostate cancer (mCRPC).

Genitourinary (Prostate) Cancer
Session Type and Session Title: 
Oral Abstract Session, Genitourinary (Prostate) Cancer
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 5007)
Andrew J. Armstrong, Bertrand Tombal, Cora N. Sternberg, Celestia S. Higano, Dana E. Rathkopf, Yohann Loriot, Fred Saad, Anthony M. Joshua, Johann Sebastian De Bono, Peter M. Venner, Joan Carles, Paul N. Mainwaring, Christopher P. Evans, Sarah B. Noonberg, Harry H. Mansbach, Suman Bhattacharya, Frank Perabo, De Phung, Tomasz M. Beer; Duke University, Durham, NC; Division of Urology, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Hospital San Camillo-Forlanini, Rome, Italy; Fred Hutchinson Cancer Research Center, Seattle, WA; Memorial Sloan Kettering Cancer Center, New York, NY; Department of Cancer Medicine, INSERM U981, Gustave Roussy, Cancer Campus, Grand Paris, Villejuif, France; University of Montréal Hospital Center, CRCHUM, Montréal, QC, Canada; Princess Margaret Hospital, University Health Network, Toronto, ON, Canada; Division of Cancer Therapeutics and Division of Clinical Studies, The Institute of Cancer Research; Drug Development Unit, The Royal Marsden NHS Foundation Trust, Surrey, United Kingdom; Cross Cancer Institute, Edmonton, AB, Canada; Hospital Universitari Vall d´Hebron, Barcelona, Spain; ICON Cancer Care, South Brisbane, Australia; University of California, Davis, Sacramento, CA; Medivation, Inc., San Francisco, CA; Astellas Pharma Global Development, Inc., Northbrook, IL; Astellas Pharma Global Development, Inc., Leiderdorp, Netherlands; Oregon Health & Science University, OHSU Knight Cancer Institute, Portland, OR

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: Enzalutamide (ENZ), an androgen receptor inhibitor, improved overall survival (OS) in men with mCRPC who had received prior docetaxel therapy (Scher, N Engl J Med 2012;367:13). The PREVAIL study examined whether ENZ could prolong OS and radiographic progression-free survival (rPFS) in men with mCRPC who had progressed on androgen deprivation therapy (ADT). Methods: In this randomized double-blind, placebo-controlled, multinational study (NCT01212991), asymptomatic or mildly symptomatic patients were randomized 1:1 to ENZ 160 mg/day or placebo (PBO). OS and rPFS were co-primary endpoints and analyzed for the intent-to-treat population. Key prespecified secondary and exploratory endpoints are noted in the table below. Results: 872 men were randomized to ENZ and 845 to PBO, with respective median treatment durations of 16.6 and 4.6 months. Based on a planned interim analysis at 540 deaths the Data Monitoring Committee recommended stopping the study and crossing PBO patients to ENZ. Efficacy results are shown in the Table. The most common adverse events with a higher incidence in the ENZ arm than PBO were fatigue (35.6% vs 25.8%), back pain (27.0% vs 22.2%), constipation (22.2% vs 17.2%), and arthralgia (20.3% vs 16.0%). Seizure was reported in 1 patient in each treatment arm (0.1%). Conclusions: In men with mCRPC who progress on ADT, treatment with enzalutamide has a favorable safety profile and significantly improves OS, rPFS, and secondary measures of disease response and progression. Clinical trial information: NCT01212991.

Co-primary endpoints Est. median (95% CI) months
HR (95% CI) P value
OS 32.4 (31.5, NYR) 30.2 (28, NYR) 0.71 (0.60, 0.84) < 0.0001
rPFS NYR (13.8, NYR) 3.9 (3.7, 5.4) 0.19 (0.15, 0.23) < 0.0001
Other efficacy endpoints
Time to cytotoxic chemotherapy 0.35 (0.30, 0.40) < 0.0001
Time to antineoplastic treatmenta 0.27 (0.24, 0.31) < 0.0001
Time to first SRE 0.72 (0.61, 0.84) < 0.0001
Time to PSA progression 0.17 (0.15, 0.20) < 0.0001
Time to FACT-P degradation 0.63 (0.54, 0.72) < 0.0001
Best objective response (CR+PR) ENZ = 58.8%
PBO = 5.0%
< 0.0001
PSA decline from baseline ENZ PBO
≥ 50% 78.0% 3.5% < 0.0001
≥ 90% 46.8% 1.2% < 0.0001

a Cytotoxic, hormonal, or investigational therapy.