Dr Shore on the Background and Outcomes of the EMBARK Trial in nmCSPC

Neal Shore, MD, FACS, United States chief medical officer, Surgery and Oncology, GenesisCare USA, medical director, Carolina Urologic Research Center, discusses the design and methodology of the phase 3 EMBARK study (NCT02319837) of enzalutamide (Xtandi), highlighting the key efficacy findings from the investigation in patients with nonmetastatic castration-sensitive prostate cancer (nmCSPC).

Notably, the FDA approved enzalutamide for patients with nmCSPC and biochemical recurrence at high risk for metastasis on November 17, 2023, based on data from the EMBARK trial. This investigation was a worldwide, prospective trial with 3 arms and enrolled 1068 patients who had previously undergone prostatectomy, with or without radiation therapy, for localized disease, Shore begins. The focus of EMBARK was on patients experiencing biochemical recurrence, characterized by prostate-specific antigen doubling times of 9 months or less, he explains. One arm of the trial (n = 358) encompassed patients who received standard luteinizing hormone–releasing hormone (LHRH) therapy plus a placebo, he states. The second arm (n = 355) included patients who received LHRH therapy plus 160 mg of enzalutamide, the approved dosage of the agent across its approval continuum, Shore adds. Furthermore, the third arm (n = 355) received open-label enzalutamide monotherapy at 160 mg daily.

Patients receiving LHRH were blinded, unlike those receiving enzalutamide monotherapy, Shore continues. The primary end point of EMBARK was metastasis-free survival (MFS), defined as the time to radiographic progression and/or death from any cause, he says. After more than 8 years of patient data collection, including evaluations at the 3- and 5-year milestones, findings revealed that the combination arm outperformed the LHRH placebo arm in terms of MFS, with an HR of 0.42 (95% CI, 0.30-0.61; P < .001), translating to a 58% enhancement in MFS, Shore emphasizes.

Although overall survival data have not yet reached statistical significance, EMBARK shows a clear trend favoring enzalutamide over LHRH alone, supported by confidence intervals already below 1, he adds. The enzalutamide monotherapy arm showed superiority over the LHRH arm, with an HR for metastasis or death of 0.63 (95% CI, 0.46-0.87; P = .005), equating to a 37% improvement in MFS, Shore concludes.