Dr. Shore presents practice-changing data in prostate cancer

The three-arm EMBARK study of leuprolide acetate (LA) plus enzalutamide (combo) vs. enzalutamide monotherapy (enza) vs. LA + placebo in patients with biochemically recurrent prostate cancer (BCR) showed statistically significant and clinically significant improvement in metastasis-free survival (MFS), risk of prostate-specific antigen (PSA) progression and time to first use of a new neoplastic agent.

The trial is potentially practice-changing for the specialty of urology.

“Enzalutamide in combination with leuprolide, if approved in this setting, has the potential to become a new standard of care for patients with high-risk BCR,” said Neal D. Shore, MD, medical director of the Carolina Urologic Research Center/GenesisCare U.S.

Up to 50% of patients experience BCR characterized by rising PSA within 10 years following definitive therapy for prostate cancer, Dr. Shore said during the Plenary session on Saturday. Patients with high-risk BCR have an increased risk of mortality.

EMBARK was a randomized, phase 3 trial in patients at high-risk, defined as a PSA-doubling time of ≤9 months and PSA ≥2 ng/mL above nadir post-radiotherapy or ≥1 ng/mL after radical prostatectomy with or without radiotherapy. Patients were randomized to enza 160 mg/day + LA, placebo + LA or enza monotherapy. 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. The primary endpoint was metastasis-free survival. Key secondary endpoints included MFS for enza mono vs. placebo + LA, time to PSA progression, time to antineoplastic therapy and overall survival (OS).

A total of 1,068 patients were randomized 1:1:1 and followed for a median of 60.7 months. Patients were a median of 69 years of age, 83% Caucasian, 7% Asian and 4.5% Black. A third had prior hormonal therapy and 76% had PSA ≤10.

MFS for enza + LA and enza mono were significantly better than placebo +LA, HR=0.43 (95% CI 0.30-0.61; p<0.0001) and HR=0.63 (95% CI 0.46–0.87; p=0.0049), respectively. There were statistically significant improvements in risk of PSA progression, enza + LA HR=0.07 (95% CI, 0.03–0.14), enza mono HR=0.33 (5% CI, 0.23–0.49; both p<0.0001) and time to first new antineoplastic therapy, enza + LA HR=0.36 (HR 0.36; 95% CI, 0.26–0.49) and enza mono HR=0.54 (95% CI, 0.41–0.71; both p<0.0001).

Median overall survival has not yet been seen, Dr. Shore reported. Interim OS trended to favor enza + LA HR=0.59 (95% CI, 0.38–0.90; p=0.0142) and enza mono HR=0.77 (95% CI, 0.51–1.15; p=0.1963) but did not reach statistical significance.

Nearly all patients reported adverse events, most commonly fatigue and hot flashes. There were no new safety signals seen in the trial and adverse events and the enza safety profile were consistent with previous clinical studies.

See The Journal of Urology® for more information on the EMBARK study.