Primary analysis of the phase 3 EMBARK trial reported efficacy and safety outcomes for enzalutamide monotherapy in patients with high-risk biochemical recurrence. Here, we report secondary endpoints for enzalutamide monotherapy vs leuprolide alone.
Patients were randomized (1:1:1) to enzalutamide plus leuprolide, leuprolide alone, or enzalutamide monotherapy. Overall survival was a key secondary endpoint; non-key secondary endpoints were time to: distant metastasis, symptomatic progression, first symptomatic skeletal event, and resumption of any hormonal therapy. Sexual health was assessed using the Quality of Life Questionnaire-Prostate 25. Time-to-event endpoints were summarized using Kaplan-Meier methods with nominal P-values.
Five-year probability rates (95% CI) for enzalutamide monotherapy vs leuprolide alone were: overall survival: 89.5% [85.6-92.4] vs 87.2% [83.0-90.4]); time to remaining free from distant metastasis: 86.8% [82.3-90.2] vs 81.5% [76.3-85.7], symptomatic progression: 66.6% [61.2-71.4] vs 53.3% [47.6-58.6], and first symptomatic skeletal event: 95.8% [92.9-97.6] vs 91.5% [87.8-94.1]. Following treatment suspension, the 5-year probability rate (95% CI) of remaining free from resumption of any hormonal therapy for leuprolide alone vs enzalutamide monotherapy was 7.8% [4.4-12.3] vs 5.6% [3.3-8.8]). Sexual health was better preserved in patients treated with enzalutamide monotherapy than leuprolide alone (HR 0.76; 95% CI 0.62-0.94; P=0.008). Following discontinuation, most patients were subsequently treated with hormonal therapies in both groups.
Secondary endpoint results support enzalutamide monotherapy as a potential option to improve efficacy and preserve sexual health vs leuprolide alone for patients with high-risk biochemical recurrence.
NCT02319837.
The Journal of urology. 2025 Dec 05 [Epub ahead of print]
Neal D Shore, Ugo De Giorgi, Ronald F Tutrone, James L Bailen, Erik Pm Roos, Ján Kliment, Gavin Marx, Lawrence I Karsh, Miguel Ramirez-Backhaus, Edward M Uchio, Stéphane Supiot, Yiyun Tang, Brad Rosbrook, Gabriel P Haas, Matt Rosales, Fabian Zohren, Jamal Tarazi, Stephen J Freedland
START Carolinas/Carolina Urologic Research Center, Myrtle Beach, South Carolina., Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy., Clinical Research, United Urology Group, Towson, Maryland., Clinical Research, CUSP LLC Research Consortium, Jeffersonville, Indiana., Department of Urology, Antonius Ziekenhuis, Sneek, Netherlands., Department of Urology, Univerzitna nemocnica Martin, Martin, Slovakia., Australian National University, Wahroonga, New South Wales, Australia., AdventHealth Urology Denver, Denver, Colorado., Servicio de Urología, Fundación Instituto Valenciano de Oncología, Valencia, Spain., Department of Urology, University of California, Irvine Medical Center, Orange, California., Institut de Cancérologie de l'Ouest, Saint-Herblain, France., Global Product Development, Pfizer Inc., South San Francisco, California., Global Product Development, Pfizer Inc., La Jolla, California., Global Product Development, Astellas Pharma Inc., Northbrook, Illinois., Astellas Pharma Global Development, Northbrook, Illinois., Global Product Development, Pfizer Inc., Cambridge, Massachusetts., Global Product Development, Pfizer Inc., Collegeville, Pennsylvania., Department of Urology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.