• Stephen J Freedland, Murilo de Almeida Luz, Ugo De Giorgi, Martin Gleave, Geoffrey T Gotto, Christopher M Pieczonka, Gabriel P Haas, Choung-Soo Kim, Miguel Ramirez-Backhaus, Antti Rannikko, Jamal Tarazi, Swetha Sridharan, Jennifer Sugg, Yiyun Tang, Ronald F Tutrone, Balaji Venugopal, Arnauld Villers, Henry H Woo, Fabian Zohren, and Neal D Shore.
• From the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles (S.J.F.); the Durham Veterans Affairs Health Care System, Durham, NC (S.J.F.); the Division of Urologic Oncology, Erasto Gaertner Hospital, Curitiba, Brazil (M.A.L.); IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori, Meldola, Italy (U.D.G.); the Vancouver Prostate Centre, University of British Columbia, Vancouver (M.G.), and the Southern Alberta Institute of Urology, University of Calgary, Calgary (G.T.G.) - both in Canada; U.S. Urology Partners and Associated Medical Professionals of New York, Syracuse (C.M.P.); Global Development (G.P.H.) and Biostatistics (J.S.), Astellas Pharma, Northbrook, IL; Ewha Womans University Mokdong Hospital, Seoul, South Korea (C.-S.K.); Servicio de Urología, Fundación Instituto Valenciano de Oncología, Valencia, Spain (M.R.-B.); the Department of Urology and Research Program in Systems Oncology, University of Helsinki, and Helsinki University Hospital - both in Helsinki, Finland (A.R.); Global Product Development, Pfizer, Collegeville, PA (J.T.); the Department of Radiation Oncology, Calvary Mater Newcastle, Waratah, NSW (S.S.), the Prostate Centre of Excellence, Sydney Adventist Hospital, Sydney, NSW (H.H.W.), and the College of Health and Medicine, Australian National University, Canberra, ACT (H.H.W.) - all in Australia; Global Product Development, Pfizer, San Francisco (Y.T.); Chesapeake Urology Research Associates, Towson, MD (R.F.T.); the Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, United Kingdom (B.V.); the Department of Urology, University of Lille, Claude Huriez Hospital, Centre Hospitalier Universitaire Lille, Lille, France (A.V.); Global Product Development, Pfizer, Cambridge, MA (F.Z.); and the Carolina Urologic Research Center and GenesisCare US, Myrtle Beach, SC (N.D.S.).
• N. Engl. J. Med. 2023 Oct 19; 389 (16): 145314651453-1465.

BackgroundPatients with prostate cancer who have high-risk biochemical recurrence have an increased risk of progression. The efficacy and safety of enzalutamide plus androgen-deprivation therapy and enzalutamide monotherapy, as compared with androgen-deprivation therapy alone, are unknown.MethodsIn this phase 3 trial, we enrolled patients with prostate cancer who had high-risk biochemical recurrence with a prostate-specific antigen doubling time of 9 months or less. Patients were randomly assigned, in a 1:1:1 ratio, to receive enzalutamide (160 mg) daily plus leuprolide every 12 weeks (combination group), placebo plus leuprolide (leuprolide-alone group), or enzalutamide monotherapy (monotherapy group). The primary end point was metastasis-free survival, as assessed by blinded independent central review, in the combination group as compared with the leuprolide-alone group. A key secondary end point was metastasis-free survival in the monotherapy group as compared with the leuprolide-alone group. Other secondary end points were patient-reported outcomes and safety.ResultsA total of 1068 patients underwent randomization: 355 were assigned to the combination group, 358 to the leuprolide-alone group, and 355 to the monotherapy group. The patients were followed for a median of 60.7 months. At 5 years, metastasis-free survival was 87.3% (95% confidence interval [CI], 83.0 to 90.6) in the combination group, 71.4% (95% CI, 65.7 to 76.3) in the leuprolide-alone group, and 80.0% (95% CI, 75.0 to 84.1) in the monotherapy group. With respect to metastasis-free survival, enzalutamide plus leuprolide was superior to leuprolide alone (hazard ratio for metastasis or death, 0.42; 95% CI, 0.30 to 0.61; P<0.001); enzalutamide monotherapy was also superior to leuprolide alone (hazard ratio for metastasis or death, 0.63; 95% CI, 0.46 to 0.87; P = 0.005). No new safety signals were observed, with no substantial between-group differences in quality-of-life measures.ConclusionsIn patients with prostate cancer with high-risk biochemical recurrence, enzalutamide plus leuprolide was superior to leuprolide alone with respect to metastasis-free survival; enzalutamide monotherapy was also superior to leuprolide alone. The safety profile of enzalutamide was consistent with that shown in previous clinical studies, with no apparent detrimental effect on quality of life. (Funded by Pfizer and Astellas Pharma; EMBARK ClinicalTrials.gov number, NCT02319837.).Copyright © 2023 Massachusetts Medical Society.

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