Dr Freedland on the FDA Approval of Enzalutamide in nmCSPC

Stephen J. Freedland, MD, Warschaw Robertson Law Families Chair in Prostate Cancer; director, Center for Integrated Research in Cancer and Lifestyle; co-director, Cancer Genetics and Prevention Program; associate director, Training and Education, Samuel Oschin Comprehensive Cancer Institute; professor, Department of Urology, Cedars-Sinai, discusses the significance of the FDA approval of enzalutamide (Xtandi) for patients with nonmetastatic castration-sensitive prostate cancer (nmCSPC).

On November 17th, 2023, the FDA approved enzalutamide with or without gonadotropin-releasing hormone analog therapy for the treatment of patients with nmCSPC who have biochemical recurrence at high risk for metastasis. This regulatory decision was supported by findings from the international phase 3 EMBARK trial (NCT02319837), in which the addition of enzalutamide to leuprolide produced a 58% reduction in the risk of metastasis or death vs leuprolide plus placebo (HR, 0.42; 95% CI, 0.30-0.61; P < .001).

At a median follow-up of 60.7 months, enzalutamide demonstrated a significant improvement in metastasis-free survival (MFS) compared with placebo in this population. The median MFS was not yet reached (NR) in the enzalutamide arm, with 92.9% and 87.3% 3-year and 5-year MFS rates, respectively. In the placebo arm, the median MFS was NR with 83.5% and 71.4% 3-year and 5-year MFS rates, respectively. These findings highlight the sustained benefit of enzalutamide in delaying metastasis in patients with nmCRPC over an extended follow-up period.

The EMBARK study addresses a longstanding unmet need in advanced prostate cancer, particularly for patients with high-risk biochemical recurrence, Freedland states. For years, managing this disease state has been complex due to a limited arsenal of effective treatment options. Hormonal therapies were often the only treatment option for patients with rapid disease progression, Freedland adds.

Overall, the approval of enzalutamide provides clinicians with an effective therapy that can delay progression in a patient population where treatment choices were previously limited, Freedland says. The results not only offer tangible hope and improved outcomes for patients, but also instill confidence in physicians by demonstrating the efficacy of addressing this disease state with a more targeted therapeutic approach, he concludes.