The enzalutamide/leuprolide combo also led to statistically significant improvements in time to PSA progression and time to start of new antineoplastic therapy.
Adding enzalutamide (Xtandi) to leuprolide significantly improved metastasis-free survival (MFS) vs leuprolide alone in patients with nonmetastatic hormone-sensitive prostate cancer (nmHSPC) and high-risk biochemical recurrence (BCR), according to topline findings from the phase 3 EMBARK trial (NCT02319837).1
Treatment with the enzalutamide/leuprolide regimen also led to statistically significant improvements in time to PSA progression and time to start of new antineoplastic therapy. A positive trend in overall survival (OS) with the combination was also observed, and researchers are continuing patient follow-up for a final OS analysis.
Pfizer and Astellas, the co-developers of enzalutamide, reported in a press release that the data from the trial will be shared at an upcoming medical conference and the companies will be communicating with the FDA about filing for a new indication for enzalutamide in this setting.
"While current treatment options for localized prostate cancer are intended to be curative, some men remain at higher risk for biochemical recurrence following primary treatment, which may result in metastases," Ahsan Arozullah, MD, MPH, senior vice president and head of Development Therapeutic Areas, Astellas, stated in the press release. The EMBARK trial is the first study to demonstrate a statistically significant improvement in MFS using the combination of Xtandi plus leuprolide in men with this stage of disease."
The double-blinded phase 3 EMBARK trial enrolled 1068 patients with nmHSPC and high-risk biochemical recurrence. Patients were accrued at clinical sites in the United States, Canada, Europe, South America, and the Asia-Pacific region.
According to the study design, “Patients who were considered high-risk BCR had a prostate-specific antigen (PSA) doubling time ≤ 9 months, serum testosterone ≥ 150 ng/dL (5.2 nmol/L), and screening PSA by the central laboratory ≥ 1 ng/mL if they had a radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer or at least 2 ng/mL above the nadir if they had radiotherapy only as primary treatment for prostate cancer.”
The overall study included 3 arms: Patients were randomized to enzalutamide plus leuprolide, enzalutamide alone, or placebo plus leuprolide. MFS was the primary end point of the trial.
Results of the study showed that patients receiving single-agent enzalutamide also had a statistically significant improvement in MFS compared with patients treated with placebo plus placebo plus leuprolide.
Thus far, there have been no new safety signals in the EMBARK trial compared with the safety profile observed with enzalutamide in previous research.
Enzalutamide currently has FDA-approved indications for metastatic castration-sensitive prostate cancer, metastatic castration-resistant prostate cancer (CRPC), and nonmetastatic CRPC.
"As the only novel hormone therapy approved for three disease states of prostate cancer in the United States, Xtandi has impacted hundreds of thousands of men," Chris Boshoff, MD, PhD, chief development officer, Oncology and Rare Disease, Pfizer Global Product Development, stated in the press release. "The topline findings from EMBARK are highly encouraging and we look forward to engaging with health authorities to potentially bring Xtandi to men with non-metastatic hormone-sensitive prostate cancer with high-risk biochemical recurrence."
1. Phase 3 Study Shows XTANDI® (enzalutamide) plus Leuprolide Significantly Improves Metastasis-Free Survival in Men with Non-Metastatic Prostate Cancer. Published online March 16, 2023. Accessed March 17, 2023. https://prn.to/42mg8QD.