The FDA sets a Prescription Drug User Fee Act date in the fourth quarter of 2023 for its decision regarding enzalutamide as a treatment for those with non-metastatic hormone-sensitive prostate cancer with a high-risk of biochemical recurrence.
The FDA has granted priority review to a supplemental new drug application (sNDA) for enzalutamide (Xtandi) for the treatment of non-metastatic hormone-sensitive prostate cancer (HSPC) at high-risk of biochemical recurrence (BCR), according to a press release from Pfizer Inc and Astellas Pharma Inc.1
The regulatory agency set a Prescription Drug User Fee Act date for the fourth quarter of 2023 for enzalutamide in this indication.
Supporting data for the sNDA came from the phase 3 EMBARK trial (NCT02319837), in which enzalutamide in combination with leuprolide significantly reduced the risk of recurrence or death by 58% compared with placebo plus leuprolide (HR, 0.42; 95% CI, 0.30-0.61; P <.0001). In terms of safety, investigators most frequently observed fatigue, hot flush, and arthralgia in those receiving enzalutamide plus leuprolide. The most common adverse effects among patients receiving enzalutamide monotherapy included fatigue, gynecomastia, and arthralgia.
According to data that read out in a plenary session at the 2023 American Urological Association’s Annual Meeting (AUA), treatment with enzalutamide plus leuprolide significantly reduced the progression risk of initiating new antineoplastic therapy by 64% compared with placebo plus leuprolide (HR, 0.36; 95% CI, 0.26-0.49; P <.0001).2 Additionally, investigators noted a 46% reduction in the progression risk of new antineoplastic therapy with enzalutamide alone vs placebo plus leuprolide (HR, 0.54; 95% CI, 0.41-0.71; P <.0001).
Investigators are discussing findings from the EMBARK trial with other regulatory bodies across the world in support of other potential approvals for enzalutamide in this population.
“[BCR] can be one of the first indicators that prostate cancer is returning or will spread, particularly among those patients [who] experience rapid prostate-specific antigen [PSA] doubling times,” Ahsan Arozullah, MD, MPH, senior vice president and head of Oncology Development at Astellas, said in the press release.1 “The addition of [enzalutamide] to leuprolide has shown greater clinical benefit compared [with] placebo plus leuprolide, and we look forward to working with the FDA and other global regulatory authorities to bring [enzalutamide] to these patients.”
Investigators of the double-blind, international EMBARK trial assessed 1068 patients at treatment sites in the United States, Canada, Europe, South America, and the Asia/Pacific region. Patients were randomly assigned to receive 160 mg of enzalutamide once a day plus 22.5 mg of leuprolide every 12 weeks (n = 355), enzalutamide alone (n = 355), or placebo in combination with leuprolide (n = 358).
The study’s primary end point was metastasis-free survival in the enzalutamide plus leuprolide arm vs the placebo plus leuprolide arm. Secondary end points included overall survival, time to castration resistance, time to distant metastasis, time to symptomatic progression, time to clinically relevant pain, and quality of life.
Patients 18 years and older with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, signet cell, or small cell features were eligible for enrollment on the EMBARK trial. Additional eligibility criteria included having a PSA doubling time of no higher than 9 months and serum testosterone of at least 150 ng/dL.