Dr Shore on the Rationale for the EMBARK Trial in Nonmetastatic Prostate Cancer

Neal Shore, MD, FACS, US chief medical officer, Surgery and Oncology, GenesisCare USA, the medical director, Carolina Urologic Research Center, discusses the rationale for the phase 3 EMBARK trial (NCT02319837) investigating enzalutamide (Xtandi) plus leuprolide (Eligard) in patients with nonmetastatic hormone-sensitive prostate cancer (nmHSPC) with high-risk biochemical recurrence.

Data presented at the 2023 American Urological Association Annual Meeting showed that patients who received enzalutamide plus leuprolide (n = 355) experienced a 58% reduction in the risk of metastasis or death by blinded independent central review (BICR) vs those who were treated with placebo plus leuprolide (n = 358; HR, 0.42; 95% CI, 0.31-0.61; P < .0001).

Although patients with nmHSPC could undergo radical prostatectomy, external beam radiation therapy, or surgery with either adjuvant or salvage radiation therapy, these methods are not always curative, Shore begins. Biochemical relapse occurs when a patient’s prostate-specific antigen (PSA) levels begins to rise, and prior evidence has shown that when a patient’s PSA doubling time is no more than 9 months, they have a more biologically active disease, Shore expands.

For patients with biochemical relapse, treatment options have included various hormonal manipulations, such as earlier-generation androgen receptor inhibitors, continuous or intermittent testosterone suppression, and androgen deprivation therapy (ADT), Shore explains. However, treatment patterns in this setting have been inconsistent, since there is not great level 1 evidence for these options, Shore notes.

Development for EMBARK and its protocol began in 2014, shortly after the approval of enzalutamide for the treatment of patients with metastatic castration-resistant prostate cancer. The design of EMBARK was ambitious because considerable time would be needed for results to read out, Shore says. The primary end point was metastasis-free survival, which is a composite end point of radiographic progression or death, Shore concludes.