Immature data suggest enzalutamide combination improves overall survival in patients with high-risk biochemical recurrence.
Enzalutamide (Xtandi, Astellas Pharma) plus leuprolide (Eligard, Lupron Depot) significantly reduced the risk of metastasis or death in men with non-metastatic hormone-sensitive prostate cancer (nmHSPC) with high-risk biochemical recurrence (BCR), according to results from the EMBARK trial (NCT02319837) that were presented in a session at the 2023 American Urological Association Annual Meeting.
Patients with high-risk BCR have a prostate-specific antigen doubling time (PSA-DT) that is equal to or less than 9 months; this indicates higher risk of metastasis and death.
“Some patients with BCR are at very high risk for developing metastatic disease, which can lead to a cascade of therapeutic interventions,” said primary EMBARK investigator Neal Shore, MD, FACS, US chief medical officer of Urology and Surgical Oncology, GenesisCare and director, Carolina Urologic Research Center, in a recent press release. “The clinical goal of BCR therapy is to delay cancer progression and avoid metastatic disease.”
Estimates suggest that 20% to 40% of patients with nmHSPC—also known as non-metastatic castration-sensitive prostate cancer (nmCSPC)—will experience BCR within 10 years of treatment; nearly 9 in 10 men with high-risk BCR will develop metastatic disease. Unfortunately, conventional radiological methods cannot detect these metastases.
The cancer responds to medical or surgical treatment that lowers testosterone levels, but 1 in 3 men will still die because of recurrence. The phase 3, randomized, double-blind, placebo-controlled, multi-national EMBARK trial was conducted for men with nmHSPC and high-risk BCR who initially underwent treatment with radical prostatectomy, radiotherapy, or both.
Investigators randomized 1068 of these patients to receive enzalutamide at 160 mg daily plus leuprolide, monotherapy with enzalutamide at 160 mg, or placebo plus leuprolide; patients in all groups were administered leuprolide at 22.5 mg every 12 weeks. The primary endpoint was metastasis-free survival (MFS), which was defined as duration of time between randomization and the earliest objective evidence of radiographic progression by central imaging or death, for enzalutamide plus leuprolide versus placebo plus leuprolide.
Enzalutamide monotherapy met the primary endpoint, reducing the risk of metastasis or death by 37% versus leuprolide plus placebo. Enzalutamide plus leuprolide reduced risk of PSA progression by 93% and monotherapy enzalutamide reduced risk by 67%. Further, immature data suggest enzalutamide combination improves overall survival (OS).
The most common adverse events (AEs) associated with enzalutamide and leuprolide treatment included fatigue, hot flash, and arthralgia. For enzalutamide monotherapy, the most commonAEs were fatigue, arthralgia, and gynecomastia.
"If approved, we hope to bring a new option to men earlier in the course of their disease," said co-principal investigator Stephen J. Freedland, MD, director of the Center for Integrated Research in Cancer and Lifestyle and the Warschaw Robertson Law Families Chair in Prostate Cancer at Cedars-Sinai Cancer, in the press release.
XTANDI® (enzalutamide) plus Leuprolide Reduced the Risk of Metastasis by 58% in Non-Metastatic Hormone-Sensitive Prostate Cancer versus Placebo plus Leuprolide. News Release. April 29, 2023. Accessed on May 1, 2023. https://www.prnewswire.com/news-releases/xtandi-enzalutamide-plus-leuprolide-reduced-the-risk-of-metastasis-by-58-in-non-metastatic-hormone-sensitive-prostate-cancer-versus-placebo-plus-leuprolide-301811445.html