LBA02-09 EMBARK: A PHASE 3 RANDOMIZED STUDY OF ENZALUTAMIDE OR PLACEBO PLUS LEUPROLIDE ACETATE AND ENZALUTAMIDE MONOTHERAPY IN HIGH-RISK BIOCHEMICALLY RECURRENT PROSTATE CANCER (2023)

You have accessJournal of UrologyCME1 Apr 2023LBA02-09 EMBARK: A PHASE 3 RANDOMIZED STUDY OF ENZALUTAMIDE OR PLACEBO PLUS LEUPROLIDE ACETATE AND ENZALUTAMIDE MONOTHERAPY IN HIGH-RISK BIOCHEMICALLY RECURRENT PROSTATE CANCERis corrected byLBA02-09 EMBARK: A Phase 3 Randomized Study of Enzalutamide or Placebo Plus Leuprolide Acetate and Enzalutamide Monotherapy in High-risk Biochemically Recurrent Prostate Cancer Neal D. Shore, Murilo de Almeida Luz, Ugo De Giorgi, Martin Gleave, Geoffrey T. Gotto, Gabriel P. Haas, 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 Stephen J. Freedland Neal D. ShoreNeal D. Shore , Murilo de Almeida LuzMurilo de Almeida Luz , Ugo De GiorgiUgo De Giorgi , Martin GleaveMartin Gleave , Geoffrey T. GottoGeoffrey T. Gotto , Gabriel P. HaasGabriel P. Haas , Miguel Ramirez-BackhausMiguel Ramirez-Backhaus , Antti RannikkoAntti Rannikko , Jamal TaraziJamal Tarazi , Swetha SridharanSwetha Sridharan , Jennifer SuggJennifer Sugg , Yiyun TangYiyun Tang , Ronald F. TutroneRonald F. Tutrone , Balaji VenugopalBalaji Venugopal , Arnauld VillersArnauld Villers , Henry H. WooHenry H. Woo , Fabian ZohrenFabian Zohren , and Stephen J. FreedlandStephen J. Freedland View All Author Informationhttps://doi.org/10.1097/JU.0000000000003361.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Within 10 years following definitive therapy for prostate cancer, ∼20 −50% of patients (pts) experience biochemical recurrence (BCR) characterized by rising prostate-specific antigen (PSA) levels. Pts with high-risk BCR have an increased risk of mortality and improved therapies are needed. The objective of EMBARK was to evaluate the efficacy and safety of enzalutamide (enza) + androgen deprivation therapy (ADT) and enza monotherapy (mono) in pts with high-risk BCR. METHODS: EMBARK is a randomized, phase 3 study of pts with BCR considered high-risk: PSA doubling time ≤9 months and PSA ≥2 ng/mL above nadir post-radiotherapy (RT) or ≤1 ng/mL after radical prostatectomy (RP) postoperative RT. Pts were randomized (1:1:1) to enza 160 mg/day + leuprolide acetate (LA) (double-blind), placebo (pbo) + LA (double-blind), or enza mono (open-label). LA 22.5 mg was administered every 12 weeks. If the PSA at week 36 was <0.2 ng/mL, therapy was stopped at week 37 and restarted when PSA was ≥2 ng/mL for pts with primary RP, and ≥5 ng/mL for pts without RP. The primary endpoint, determined by blinded, independent central review (BICR), was metastasis-free survival (MFS) with enza + LA vs pbo + LA. Key secondary endpoints were MFS of enza mono vs pbo + LA, time to PSA progression, time to antineoplastic therapy, and overall survival (OS) of enza + LA or enza mono vs pbo + LA. RESULTS: 1068 pts were randomized into the study (enza + LA, n=355; pbo + LA, n=358; enza mono, n=355). After median follow-up of 60.7 months, per BICR, MFS for enza + LA (HR 0.42; 95% CI 0.30 −0.61; p<0.0001) and enza mono (HR 0.63; 95% CI 0.46 −0.87; p=0.0049) were statistically superior to pbo + LA. Statistically significant improvements were also observed in risk of PSA progression (enza + LA: HR 0.07; 95% CI, 0.03 −0.14; enza mono: HR 0.33; 95% CI, 0.23 -0.49; both p<0.0001) and time to first use of new antineoplastic therapy (enza + LA: HR 0.36; 95% CI, 0.26 −0.49; enza mono: HR 0.54; 95% CI, 0.41 −0.71; both p<0.0001). Interim OS data trended in favor enza + LA (HR 0.59; 95% CI, 0.38 −0.90; p=0.0142, did not cross interim efficacy boundary) and enza mono (HR 0.77; 95% CI, 0.51 −1.15; p=0.1963). Fatigue and hot flash were the most common adverse events; no new safety signals were observed. CONCLUSIONS: In pts with high-risk BCR, enza + ADT and enza mono demonstrated a statistically significant and clinically meaningful improvement in MFS vs pbo + ADT. The safety profile of enza was consistent with results from previous clinical studies. CLINICAL TRIAL REGISTRATION NUMBER: NCT02319837. Source of Funding: Pfizer Inc. and Astellas Pharma Inc © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of Urology2 May 2023LBA02-09 EMBARK: A Phase 3 Randomized Study of Enzalutamide or Placebo Plus Leuprolide Acetate and Enzalutamide Monotherapy in High-risk Biochemically Recurrent Prostate Cancer Volume 209Issue Supplement 4April 2023Page: e1190 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Neal D. Shore More articles by this author Murilo de Almeida Luz More articles by this author Ugo De Giorgi More articles by this author Martin Gleave More articles by this author Geoffrey T. Gotto More articles by this author Gabriel P. Haas More articles by this author Miguel Ramirez-Backhaus More articles by this author Antti Rannikko More articles by this author Jamal Tarazi More articles by this author Swetha Sridharan More articles by this author Jennifer Sugg More articles by this author Yiyun Tang More articles by this author Ronald F. Tutrone More articles by this author Balaji Venugopal More articles by this author Arnauld Villers More articles by this author Henry H. Woo More articles by this author Fabian Zohren More articles by this author Stephen J. Freedland More articles by this author Expand All Advertisement PDF downloadLoading ...