Adding enzalutamide to ADT cuts risk for metastasis by 58% in prostate cancer subgroup
Key takeaways:
- Enzalutamide plus leuprolide and enzalutamide alone significantly extended MFS vs. leuprolide and placebo.
- Groups that received enzalutamide also exhibited a significant reduction in risk for PSA progression.
The addition of enzalutamide to androgen deprivation therapy extended metastasis-free survival among men with nonmetastatic, hormone-sensitive prostate cancer with high-risk biochemical recurrence, according to study results.
The findings of the randomized, phase 3 EMBARK study, presented during American Urological Association Annual Meeting, also showed a statistically significant and clinically meaningful metastasis-free survival (MFS) benefit with enzalutamide (Xtandi; Astellas Pharma, Pfizer) as monotherapy vs. placebo and ADT. The androgen receptor signaling inhibitor also had a safety profile consistent with that observed in previous studies, the abstract stated.
“There are patients with localized prostate cancer who undergo prostatectomy or radiation therapy in an attempt to cure their disease, but, unfortunately, some patients will develop [biochemical recurrence],” Neal D. Shore, MD, FACS, chief medical officer of urology and surgical oncology at GenesisCare and director of Carolina Urologic Research Center, said in an Astellas/Pfizer press release. “Importantly, some patients with [biochemical recurrence] are at very high risk for developing metastatic disease, which can lead to a cascade of therapeutic interventions.”
Methodology
In the international EMBARK study, Shore and colleagues evaluated the safety and efficacy of enzalutamide, both added to ADT with leuprolide and as monotherapy, among 1,068 men with nonmetastatic, hormone-sensitive prostate cancer considered to experience high-risk biochemical recurrence. The researchers randomly assigned patients to 160 mg daily enzalutamide with leuprolide (n = 355), placebo and leuprolide (n = 358) or enzalutamide monotherapy (n = 355). Patients received leuprolide dosed at 22.5 mg every 12 weeks.
MFS with enzalutamide and leuprolide vs. placebo and leuprolide according to blinded independent central review served as the primary endpoint. Secondary endpoints included MFS with enzalutamide monotherapy vs. placebo and leuprolide, time to PSA progression, time to antineoplastic therapy and OS.
Median follow-up was 60.7 months.
Results
Researchers reported a statistically significant MFS benefit with both enzalutamide and leuprolide (HR = 0.42; 95% CI, 0.3-0.61) and enzalutamide monotherapy (HR = 0.63; 95% CI, 0.46-0.87) compared with placebo and leuprolide. The groups that received enzalutamide also exhibited a significant reduction in risk for PSA progression (combination, HR = 0.07; 95% CI, 0.03-0.14; monotherapy, HR = 0.33; 95% CI, 0.23-0.49) and improvement in time to first use of new antineoplastic therapy (combination, HR = 0.36; 95% CI, 0.26-0.49; monotherapy, HR = 0.54; 95% CI, 0.41-0.71).
Interim OS data showed positive trends favoring the enzalutamide combination group (HR = 0.59; 95% CI, 0.38-0.9) and enzalutamide monotherapy group (HR = 0.77; 95% CI, 0.51-1.15), with final OS analysis planned after longer follow-up.
The most common adverse events included fatigue, hot flush and arthralgia with the enzalutamide-leuprolide combination and fatigue, gynecomastia, and arthralgia with enzalutamide monotherapy.
Next steps
The EMBARK results will be reviewed with FDA officials and used to support a possible regulatory submission later this year for enzalutamide for this indication, according to the press release.
“The clinical goal of [biochemical recurrence] therapy is to delay cancer progression and avoid metastatic disease,” Shore said in the press release. “The MFS results from the EMBARK study demonstrate that this intervention with XTANDI plus leuprolide was statistically significant for patients with high-risk [biochemical recurrence].”
References:
- Shore ND, et al. J Urol. 2023;doi:10.1097/JU.0000000000003518.
- Xtandi (enzalutamide) plus leuprolide reduced the risk of metastasis by 58% in non-metastatic hormone-sensitive prostate cancer versus placebo plus leuprolide (Astellas Pharma/Pfizer press release). Available at: 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. Published April 29, 2023. Accessed May 1, 2023.
Collapse
Read more about