EMBARK: Enzalutamide Plus ADT, Alone in High-Risk Biochemically Recurrent Prostate Cancer

Neal Shore, MD, FACS, Carolina Urologic Research Center, presented the results of the phase 3 randomized EMBARK study as a late-breaking abstract at the American Urological Association 2023 meeting.

Dr. Shore began by stating that within 10 years following definitive therapy for prostate cancer, between 20% and 50% of patients experience biochemical recurrence (BCR) characterized by rising PSA levels, and limited level 1 clinical data exist for the treatment of these patients. Patients with high-risk BCR are at increased risk of prostate cancer-specific mortality, and previous phase 3 evidence has demonstrated that treatment intensification with androgen receptor signaling inhibitors—including enzalutamide—consistently improve patient outcomes across the prostate cancer continuum.

The objective of EMBARK—a global, multicenter, phase 3 randomized trial—was to evaluate enzalutamide in combination with leuprolide acetate and enzalutamide monotherapy in patients with high-risk BCR. A total of 1068 patients were randomized (1:1) to receive enzalutamide plus leuprolide acetate (n=355), placebo plus leuprolide acetate (n=358), or enzalutamide monotherapy (n=355). Dr. Shore noted that if 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 radical prostatectomy (RP), and ≥5 ng/mL for pts without RP.

The primary endpoint—determined by blinded, independent central review—was metastasis-free survival (MFS) for enzalutamide plus leuprolide acetate versus placebo plus leuprolide acetate. Secondary endpoints included MFS for enzalutamide monotherapy versus placebo plus leuprolide acetate, time to progression, time to antineoplastic therapy, and overall survival of enzalutamide plus leuprolide acetate and enzalutamide monotherapy versus placebo plus leuprolide acetate.

After a median follow-up of 60.7 months, MFS for enzalutamide plus leuprolide acetate (hazard ratio [HR], 0.42; 95% CI, 0.30-0.61; P<.0001) and enzalutamide monotherapy (HR, 0.63; 95% CI, 0.46-0.87; P=.0049) were statistically superior to placebo plus leuprolide acetate. Additionally, Dr. Shore reported that statistically significant improvements were observed in risk of PSA progression (enzalutamide plus leuprolide acetate: HR, 0.07; 95% CI, 0.03-0.14; enzalutamide monotherapy: HR, 0.33; 95% CI, 0.23-0.49; both P<.0001) and time to first use of new antineoplastic therapy (enzalutamide plus leuprolide acetate: HR, 0.36; 95% CI, 0.26-0.49; enzalutamide monotherapy: HR, 0.54; 95% CI, 0.41-0.71; both P<.0001).

Interim overall survival data is trending in favor of enzalutamide plus leuprolide acetate and enzalutamide monotherapy, he added, noting that fatigue and hot flash were the most common adverse events for all treatment cohorts and no new safety signals have been observed to date with enzalutamide.

“Enzalutamide in combination with ADT, if approved in this setting, has the potential to become a new standard of care for patients with high-risk BCR,” Dr. Shore concluded.