Abstract 691TiP
Background
There are limited evidence-based options for men with rising prostate-specific antigen (PSA) after definitive therapy for prostate cancer (PC). In the absence of overt metastases, these nmHSPC patients often receive androgen deprivation therapy (ADT). There is no standard of care (SoC) consensus on optimal ADT timing though most men are treated prior to metastases, especially those with high-risk features, including high-grade disease [Gleason score 8-10]/short PSA doubling times [PSADT <10-12 mo]. Given data that ADT + novel hormonal agents improve survival in men with metastatic HSPC, there is a desire to test these agents even earlier in the disease course. The main objective of EMBARK is to assess whether ENZA plus LHRHa or ENZA monotherapy when given before the onset of metastases improves metastasis-free survival (MFS) vs monotherapy LHRHa in high-risk nmHSPC patients.
Trial design
EMBARK is a randomized, phase III study of high-risk nmHSPC patients with a PSADT of ≤9 mo, and screening PSA of ≥1 ng/mL post radical prostatectomy (RP) (+/- radiation therapy [RT]) or ≥2 ng/mL above nadir post-RT, and serum testosterone ≥150 ng/dL. Men will be randomized 1:1:1 to ENZA 160 mg/d plus LHRHa or placebo plus LHRHa (double-blind arms) or ENZA monotherapy (open-label). Patients have treatment suspended on wk 37 if PSA levels are <0.2 ng/mL and reinstated if levels increase to ≥2.0 ng/mL (+RP) or ≥5.0 ng/mL (-RP). Patients with PSA ≥0.2 ng/mL continue until treatment discontinuation criteria are met. The primary endpoint is MFS comparing ENZA plus LHRHa vs placebo plus LHRHa. Key secondary endpoints are MFS comparing ENZA monotherapy vs placebo plus LHRHa, time to PSA progression, time to first use of new antineoplastic therapy, and overall survival. Progression-free survival on first subsequent therapy (PFS2) is an exploratory endpoint. The study enrollment was completed on June 14, 2018 with a total of 1068 patients randomized.
Clinical trial identification
NCT02319837.
Editorial acknowledgement
Editorial assistance funded by Pfizer Inc. (New York, NY) and Astellas Pharma, Inc (Northbrook, IL), the co-developers of enzalutamide, was provided by Ira Mills, PhD and Dena McWain from Ashfield Healthcare Communications.
Legal entity responsible for the study
Pfizer Inc. and Astellas Pharma, Inc.
Funding
Pfizer Inc. and Astellas Pharma, Inc.
Disclosure
U. De Giorgi: Honoraria (institution): AstraZeneca; Honoraria (institution): Roche; Honoraria (self), Honoraria (institution): Sanofi; Honoraria (self): Astellas; Honoraria (self): Bayer; Honoraria (self), Travel/Accommodation/Expenses: BMS; Honoraria (self), Travel/Accommodation/Expenses: Ipsen; Honoraria (self), Travel/Accommodation/Expenses: Janssen; Honoraria (self): Merck; Honoraria (self), Travel/Accommodation/Expenses: Pfizer. N. Shore: Advisory/Consultancy: Bayer; Advisory/Consultancy: Janssen Scientific Affairs; Advisory/Consultancy: Dendreon; Advisory/Consultancy: Tolmar; Advisory/Consultancy: Ferring; Advisory/Consultancy: BMS; Advisory/Consultancy: Amgen; Advisory/Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Fergene; Advisory/Consultancy: Myovant Sciences; Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy: Merck; Advisory/Consultancy: Nymox; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Boston Scientific; Honoraria (institution): MDx Health. M. Gleave: Licensing/Royalties: OGX-011 & OGX-427; Licensing/Royalties: ST-POP & ST-CP. B. Rosbrook: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer, Inc. Q. Shen: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer Inc. J. Sugg: Full/Part-time employment: Asetllas Pharma Inc.; Shareholder/Stockholder/Stock options: AstraZeneca. G.P. Haas: Shareholder/Stockholder/Stock options, Full/Part-time employment: Astellas Pharma Inc. S.J. Freedland: Advisory/Consultancy, Research grant/Funding (institution): Pfizer Inc.; Advisory/Consultancy: Astellas; Advisory/Consultancy: Janssen; Advisory/Consultancy: Bayer; Advisory/Consultancy: Myovant; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Merck; Advisory/Consultancy: Dendreon; Advisory/Consultancy: Sanofi. All other authors have declared no conflicts of interest.