A phase 3 randomised study of enzalutamide plus leuprolide and enzalutamide monotherapy in high-risk non-metastatic hormone-sensitive prostate cancer with rising PSA after local therapy: EMBARK study design.

Limited data from controlled clinical trials are available for men who experience biochemical recurrence after definitive therapy for prostate cancer. In the absence of overt metastases, patients with non-metastatic castration-sensitive prostate cancer (nmCSPC) often receive androgen deprivation therapy (ADT). There is no standard-of-care consensus on optimal ADT timing, although most men are treated prior to metastases, especially those with high-risk features (Gleason score 8-10 or prostate-specific antigen doubling time (PSADT) <9-12 months). Given data that ADT plus novel hormonal agents improve survival in men with metastatic CSPC, there is a desire to evaluate these agents earlier in the disease course. The main objective of EMBARK is the comparative assessment of enzalutamide plus leuprolide (luteinising hormone-releasing hormone agonist (LHRHa)) or enzalutamide monotherapy versus monotherapy LHRHa to improve metastasis-free survival (MFS) in patients with high-risk nmCSPC PSA recurrence after definitive therapy.

EMBARK is a randomised, phase 3 study of high-risk patients with nmCSPC, a PSADT of ≤9 months and a screening PSA of ≥2 ng/mL above the nadir after radiotherapy (RT) or ≥1 ng/mL after radical prostatectomy (RP) with or without postoperative RT. Men (n=1050) are randomised 1:1:1 to enzalutamide 160 mg/day plus LHRHa or placebo plus LHRHa (double-blind arms) or enzalutamide monotherapy (open-label arm). Treatment is suspended at week 37 if PSA concentrations are <0.2 ng/mL and reinstated if levels rise to ≥2.0 ng/mL with RP or ≥5.0 ng/mL without RP. Patients with PSA ≥0.2 ng/mL at week 37 continue until treatment discontinuation criteria are met. The primary endpoint is MFS comparing enzalutamide plus LHRHa versus placebo plus LHRHa.

The study is conducted under the guiding principles of the World Medical Association Declaration of Helsinki. The results will be disseminated at research conferences and in peer-reviewed journals.

NCT02319837.

BMJ open. 2021 Aug 12*** epublish ***

Stephen J Freedland, Ugo De Giorgi, Martin Gleave, Brad Rosbrook, Qi Shen, Jennifer Sugg, Gabriel P Haas, Neal D Shore

Division of Urology, Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA ., Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy., Department of Urologic Sciences, Vancouver Prostate Centre, The University of British Columbia, Vancouver, British Columbia, Canada., Department of Global Biometrics and Data Management, Pfizer, New York, New York, USA., Department of Product Development, Pfizer, New York, New York, USA., Department of Biostatistics, Astellas Pharma US, Northbrook, Illinois, USA., Astellas Pharma Global Development, Northbrook, Illinois, USA., Carolina Urologic Research Center, Myrtle Beach, South Carolina, USA.

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