Dr Freedland on the Rationale Behind the EMBARK Trial in Prostate Cancer

"Adding an androgen receptor pathway inhibitor like enzalutamide to ADT significantly improves survival, delays progression, and has an adverse effect profile that is relatively well manageable. The question is: Can we apply that one step earlier in this high-risk, biochemical-recurrent, conventional imaging–negative patient population?”

Stephen Freedland, MD, a professor, a urologic surgeon, and the Warschaw, Robertson, Law Families Chair in Prostate Cancer Cedars-Sinai; as well as associate director of Education & Training and director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Cancer Institute, discussed the phase 3 EMBARK trial (NCT02319837) evaluating overall survival with enzalutamide (Xtandi) plus leuprolide in high-risk nonmetastatic prostate cancer progressing after radical prostatectomy, radiotherapy, or both.

Freedland stated that the rationale behind the EMBARK trial was to evaluate the already-known benefits of combining androgen receptor pathway inhibitors like enzalutamide with androgen deprivation therapy (ADT) in metastatic settings in a high-risk, biochemical-recurrent, conventional imaging–negative patient population. Data from the EMBARK trial shows that enzalutamide combined with ADT reduced the risk of death by more than 40% in the high-risk patient population compared with leuprolide alone.

Freedland highlighted key elements of EMBARK trial, noting its 3-arm design. He also explained that the primary end point of the trial was metastasis-free survival as assessed by blinded independent central review in patients with high-risk, biochemical-recurrent prostate cancer.

In the experimental arm evaluating enzalutamide plus leuprolide, patients received enzalutamide at a daily oral dose of 160 mg, administered as 4, 40-mg capsules. This regimen was combined with leuprolide delivered as a single intramuscular or subcutaneous injection every 12 weeks.

Disclosures: Freedland reported having consultant roles with Astellas Pharma Inc., AstraZeneca, Bayer, Eli Lilly, Johnson & Johnson Innovative Medicine (formerly Janssen), Merck, Novartis, Pfizer Inc., Sanofi, Sumitomo Pharma America, Inc. (formerly Myovant Sciences, Inc.), and Tolmar.