Combination treatment with enzalutamide with leuprolide is associated with improved metastasis-free survival compared with leuprolide therapy alone in patients with nonmetastatic hormone-sensitive prostate cancer (nmHSPC) who have high-risk biochemical recurrence (BCR), according to data presented at the American Urological Association’s 2023 Annual Scientific Meeting in Chicago, Illinois.

The finding is from the phase 3 EMBARK trial ( NCT02319837), which enrolled 1068 patients who had high-risk BCR after definitive therapy for prostate cancer. The investigators defined high-risk BCR as a PSA doubling time of 9 months or less, a PSA level of 1 ng/mL or higher if they had a radical prostatectomy, with or without radiation therapy, as primary treatment for prostate cancer, or a PSA level of 2 ng/mL or more above nadir for patients who had only radiation therapy as primary treatment.

The investigators, led by Neal D. Shore, MD, Director, CPI, of Carolina Urologic Research Center and practitioner at Atlantic Urology Clinics in Myrtle Beach, South Carolina, randomly assigned 355 patients to received enzalutamide (160 mg/day) plus leuprolide, 358 to placebo plus leuprolide, and 355 to enzalutamide monotherapy. The median follow-up duration was 60.7 months.

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Compared with placebo recipients, the combination arm and enzalutamide monotherapy arm had a significant 58% and 37% lower risk for metastasis, respectively, as well as a significant 93% and 67% lower risk for PSA progression, respectively, Dr Shore reported.

In addition, the combination arm and enzalutamide monotherapy arm had a 64% and 46% decreased risk, respectively, of requiring new antineoplastic therapy.

The most common adverse events were fatigue and hot flashes. The investigators reported observing no new safety signals.

Disclosure: This research was supported by Pfizer Inc. and Astellas Pharma Inc. Please see the original reference for a full list of disclosures.


Shore ND, de Almeida Luz M, de Giorgi U, et al. EMBARK: A phase 3 randomized study of enzalutamide or placebo plus leuprolide acetate and enzalutamide monotherapy in high-risk biochemically recurrent prostate cancer. Presented at: AUA 2023, Chicago, Illinois, April 28-May 1. Abstract LBA02-09.