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Sandy Srinivas, MD
Sandy Srinivas, MD
Posted: Wednesday, November 22, 2023
On November 16, 2023, the U.S. Food and Drug Administration (FDA) approved the androgen receptor blocker enzalutamide (Xtandi) for use in patients with nonmetastatic castration-sensitive prostate cancer with biochemical recurrence who are at high risk for metastasis. Enzalutamide is also indicated for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel.
Efficacy was evaluated in the randomized EMBARK trial (ClinicalTrials.gov identifier NCT02319837), which included 1,068 patients with nonmetastatic castration-sensitive prostate cancer who were at high risk of biochemical recurrence. All patients had prior definitive therapy with radical prostatectomy and/or radiotherapy with curative intent, had a prostate-specific antigen (PSA) doubling time up to 9 months, and were not candidates for salvage radiotherapy at enrollment. Patients were randomly assigned 1:1:1 to receive blinded enzalutamide at 160 mg once daily plus leuprolide, open-label single-agent enzalutamide at 160 mg once daily, or blinded placebo once daily plus leuprolide.
A statistically significant improvement in metastasis-free survival was demonstrated for enzalutamide plus leuprolide compared with placebo plus leuprolide, with a median not reached in either arm (hazard ratio [HR] = 0.42; 95% confidence interval [CI] = 0.30–0.61; P < .0001). A statistically significant improvement in metastasis-free survival was also demonstrated for enzalutamide monotherapy compared with placebo plus leuprolide (HR = 0.63; 95% CI = 0.46–0.87; P = .0049). At the time of this analysis, overall survival data were immature, with 12% deaths in the overall population.
The most common adverse reactions (≥ 20% incidence) to enzalutamide plus leuprolide were hot flush, musculoskeletal pain, fatigue, fall, and hemorrhage. The most common adverse reactions to enzalutamide monotherapy were fatigue, gynecomastia, musculoskeletal pain, breast tenderness, hot flush, and hemorrhage.
The recommended enzalutamide dose is 160 mg administered orally once daily with or without food until disease progression or unacceptable toxicity.
U.S. Food and Drug Administration
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