Enzalutamide plus leuprolide appears to improve metastases-free survival vs placebo plus leuprolide in patients with non-metastatic hormone-sensitive prostate cancer.
Enzalutamide (Xtandi) and leuprolide yielded improvement in the primary end point of metastasis-free survival (MFS) compared with placebo plus leuprolide among patients with non-metastatic hormone-sensitive prostate cancer (HSPC) at a high-risk biochemical recurrence, according to a press release on findings from the phase 3 EMBARK trial (NCT02319837).
Although the data are immature, these topline findings also included a positive trend in overall survival (OS), a key secondary end point of the study. Additionally, enzalutamide monotherapy demonstrated a clinically meaningful and statistically significant extension of MFS compared with placebo plus leuprolide. Data regarding other secondary end points, such as prostate-specific antigen (PSA) progression and time to first use of new antineoplastic therapy, have reached statistical significance. The safety profile was consistent with the established profile of enzalutamide.
Details of these findings will be released at a future medical conference.
“While current treatment options for localized prostate cancer are intended to be curative, some [patients] 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 in therapeutic areas at Astellas, said in the press release. “The EMBARK trial is the first study to demonstrate a statistically significant improvement in MFS using the combination of [enzalutamide] plus leuprolide in [patients] with this stage of disease.”
The multinational, randomized, double-blind phase 3 EMBARK trial had an actual enrollment of 1068 patients. High-risk biochemical recurrence was defined by the following criteria: a PSA doubling time of 9 months or less, serum testosterone of 150 ng/dL or greater, and screening PSA by the central laboratory of at least 1 ng/mL if they underwent a radical prostatectomy as primary treatment or at least 2 ng/mL above the nadir if they underwent radiotherapy only as their primary treatment.
Patients in the EMBARK trial were randomly assigned 1:1:1 to receive either oral enzalutamide at a dose of 160 mg once daily plus intramuscular or subcutaneous leuprolide once every 12 weeks; matched placebo plus the leuprolide regimen; or the enzalutamide capsules alone as a monotherapy.
Exclusion criteria included any prior or present evidence of distant metastases as well as any prior hormonal therapy, save for therapy to treat prostate cancer lasting 36 or fewer months and concluding no less than 9 months before randomization, or a single dose or short course of hormonal therapy to treat rising PSA no less than 9 months before randomization. Prior cytotoxic chemotherapy or systemic biologic therapy were also grounds for exclusion.
“As the only novel hormone therapy approved for 3 disease states of prostate cancer in the United States, enzalutamide has impacted hundreds of thousands of [patients],” Chris Boshoff, MD, PhD, chief development officer of oncology and rare disease at Pfizer Global Product Development, said in the press release. “The top line findings from EMBARK are highly encouraging and we look forward to engaging with health authorities to potentially bring enzalutamide to [patients] with non-metastatic [HSPC] with high-risk biochemical recurrence.”
Phase 3 study shows XTANDI® (enzalutamide) plus leuprolide significantly improves metastasis-free survival in men with non-metastatic prostate cancer. News Release. Pfizer Inc. March 16, 2023. Accessed March 17, 2023. https://bit.ly/3lprpPJ