FDA Expands Enzalutamide Approval to Earlier Prostate Cancer

Sharon Worcester, MA

November 17, 2023

The US Food and Drug Administration (FDA) has approved enzalutamide (Xtandi, Astellas and Pfizer) for men with nonmetastatic castration-sensitive prostate cancer who experience biochemical recurrence and are at high risk for metastasis.

Enzalutamide was previously approved for men with metastatic castration-sensitive prostate cancer. The current approval expands the indication for the drug to an earlier advanced prostate cancer setting.

With this new approval, enzalutamide "becomes the first and only androgen receptor signaling inhibitor approved by the FDA" to treat this earlier prostate cancer patient population, according to a press release from Astellas and Pfizer.

The approval was based on findings from the pivotal phase 3 EMBARK trial, which found a statistically significant reduction in the risk of metastasis or death among men who received enzalutamide plus the gonadotropin-releasing hormone agonist leuprolide, in comparison with placebo plus leuprolide.

The Astellas- and Pfizer-led trial enrolled 1068 patients with nonmetastatic castration-sensitive cancer who were at high risk for biochemical recurrence. Participants were randomly assigned to receive either enzalutamide 160 mg daily plus leuprolide 22.5 mg every 12 weeks (n = 355), enzalutamide as single-agent therapy (n = 355), or placebo plus leuprolide (n = 358).

The median 5-year metastasis-free survival rate was 87.3% in the enzalutamide arm, vs 71.4% in the placebo arm (hazard ratio [HR] for metastasis or death, 0.42). Single-agent enzalutamide was also associated with a significant reduction in metastasis or death in comparison with leuprolide (80.0% vs 71.4%; HR, 0.63).

Detailed results from the EMBARK trial were presented as a plenary session during the 2023 American Urological Association Annual Meeting and at the 2023 European Society of Medical Oncology, as reported by Medscape Medical News. The study was published October 19 in The New England Journal of Medicine.

Grade 3 or higher adverse events were reported in 46% of patients in the combination enzalutamide arm, 50% in the single-agent enzalutamide arm, and 43% in the placebo arm. Permanent discontinuation due to adverse events occurred 21%, 18%, and 10% of patients, respectively.

The most common adverse reactions in patients who received enzalutamide plus leuprolide were hot flush, musculoskeletal pain, fatigue, fall, and hemorrhage. No new safety signals were observed, and there were no substantial between-group differences in quality-of-life measures.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on Twitter: @SW_MedReporter.


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