The primary analysis of EMBARK reported improved metastasis-free survival for enzalutamide plus leuprolide (enzalutamide combination) vs leuprolide plus placebo (leuprolide alone) in patients with high-risk biochemical recurrence (BCR) while maintaining quality of life. Here, we present secondary efficacy endpoints for enzalutamide combination vs leuprolide alone.
EMBARK is a global, multicenter, randomized, controlled, phase 3 trial. Patients were randomized (1:1:1) to enzalutamide combination, leuprolide alone, or enzalutamide monotherapy. Non-key secondary endpoints reported herein include time to: distant metastasis, resumption of any hormonal therapy, castration resistance, symptomatic progression, and first symptomatic skeletal event. Hormonal treatment-related symptoms were assessed using the Quality of Life Questionnaire-Prostate 25. Time-to-event endpoints were summarized using the Kaplan-Meier method, with nominal P-values.
Enzalutamide combination vs leuprolide alone was associated with increased 5-year probabilities (95% CI) for remaining free of: distant metastasis (91.0% [87.1‒93.7] vs 81.5% [76.3-85.7]), resumption of any hormonal therapy after treatment suspension (14.9% [10.8-19.6] vs 7.8% [4.4-12.3]), castration resistance (96.6% [93.9-98.1] vs 67.8% [62.4-72.6]), symptomatic progression (70.9% [65.5-75.6] vs 53.3% [47.6-58.6]), and first symptomatic skeletal event (97.8% [95.4-98.9] vs 91.5% [87.8-94.1]). Time to confirmed clinically meaningful deterioration of hormonal treatment-related symptoms favored leuprolide alone vs enzalutamide combination, although the median difference was small (0.03 months).
Combined with the primary findings from EMBARK, data from non-key secondary efficacy endpoints strengthen support for enzalutamide combination as a new standard of care for patients with high-risk BCR.
NCT02319837.
The Journal of urology. 2025 Dec 09 [Epub ahead of print]
Neal D Shore, Martin Gleave, Ugo De Giorgi, Antti Rannikko, Christopher M Pieczonka, Swetha Sridharan, Klaus Brasso, Henry H Woo, Antonio Gómez Caamaño, Jeff W Saranchuk, Luke T Nordquist, Ubirajara Ferreira, 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., Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada., Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy., Department of Urology and Research Program in Systems Oncology, University of Helsinki, Helsinki, Finland., Clinical Research, US Urology Partners and Associated Medical Professionals of New York, PLLC, Syracuse, New York., Department of Radiation Oncology, Calvary Mater, Newcastle, New South Wales, Australia., Copenhagen Prostate Cancer Center, Department of Urology, Center for Cancer and Organ Diseases, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Department of Urology, Blacktown and Mount Druitt Hospitals, Blacktown,, New South Wales, Australia., Department of Radiation Oncology, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain., Manitoba Prostate Centre CancerCare, Manitoba, Winnipeg, Canada., XCancer/Urology Cancer Center, Omaha, NE, USA., Department of Urology, State University of Campinas, Campinas, Brazil., 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.