Enzalutamide Plus Leuprolide Improves MFS in Nonmetastatic Castration-Sensitive Prostate Cancer

Enzalutamide (Xtandi) plus leuprolide demonstrated a statistically significant and clinically meaningful improvement in metastasis-free survival (MFS) compared with placebo plus leuprolide in patients with nonmetastatic castration-sensitive prostate cancer with a high-risk of biochemical recurrence, meeting the primary end point of the phase 3 EMBARK trial (NCT02319837).^1,2

Topline findings also showed a positive trend in overall survival (OS), a key secondary end point, with the combination, although data were not yet mature. Patients in the trial will continue to be followed for a final OS analysis. A statistically significant and clinically meaningful improvement in MFS with enzalutamide monotherapy vs placebo plus leuprolide, another key secondary end point of the trial, was also seen.

Detailed results from the study will be presented at an upcoming medical meeting, and the data will be discussed with the FDA to support a potential regulatory submission for enzalutamide in this indication.

“As the only novel hormone therapy approved for three disease states of prostate cancer in the US, [enzalutamide] has impacted hundreds of thousands of men,” Chris Boshoff, MD, PhD, chief development officer of Oncology and Rare Disease at Pfizer Global Product Development, said in a press release. “The topline findings from EMBARK are highly encouraging and we look forward to engaging with health authorities to potentially bring [enzalutamide] to men with non-metastatic hormone-sensitive prostate cancer with high-risk biochemical recurrence.”

EMBARK is a phase 3, randomized, double-blind, placebo-controlled, multi-national trial that enrolled 1068 patients with nonmetastatic castration-sensitive prostate cancer with high-risk biochemical recurrence. The study enrolled at sites in the United States, Canada, Europe, South America, and the Asia-Pacific region.

High-risk of biochemical recurrence was defined as a prostate-specific antigen (PSA) doubling time of 9 months or less, serum testosterone at or above 150 ng/dL (5.2 nmol/L), and screening PSA by central laboratory at or above 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.

Eligible patients were randomly assigned to receive 160 mg of enzalutamide daily plus leuprolide; 160 mg of enzalutamide as a single agent; or placebo plus leuprolide.

The primary end point of the trial was MFS for enzalutamide plus leuprolide vs placebo plus leuprolide, defined as the duration of time in months between randomization and the earliest objective evidence of radiographic progression by central imaging, or death.

Other key secondary end points, including time to PSA progression and time to first use of new antineoplastic therapy, reached statistical significance. Other secondary end points, including time to castration resistance, time to distant metastasis, and quality of life, are being analyzed.

Additional results from the preliminary safety analysis indicated that no new signals have occurred to date, with enzalutamide showing similarity to its established profile as a single agent.

“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 at Astellas, said. “The EMBARK trial is the first study to demonstrate a statistically significant improvement in MFS using the combination of [enzalutamide] plus leuprolide in men with this stage of disease.”

References

1. Phase 3 study shows XTANDI® (enzalutamide) plus leuprolide significantly improves metastasis-free survival in men with non-metastatic prostate cancer. News release. Pfizer. March 16, 2023. Accessed March 16, 2023. https://www.pfizer.com/news/press-release/press-release-detail/phase-3-study-shows-xtandir-enzalutamide-plus-leuprolide
2. Safety and efficacy study of enzalutamide plus leuprolide in patients with nonmetastatic prostate cancer (EMBARK). ClinicalTrials.gov. Updated March 9, 2023. Accessed March 17, 2023. https://www.clinicaltrials.gov/ct2/show/NCT02319837