On June 3, 2025, the U.S. Food and Drug Administration (FDA) approved darolutamide (Nubeqa) for the treatment of metastatic castration-sensitive prostate cancer (mCSPC). The oral androgen receptor inhibitor had previously been approved by the FDA in combination with docetaxel for mCSPC.
Efficacy was evaluated in phase III ARANOTE trial (ClinicalTrials.gov identifier NCT02799602), a randomized, double-blind, placebo-controlled trial in 669 patients with mCSPC. Patients received either darolutamide or placebo. All patients received a gonadotropin-releasing hormone analog concurrently or had prior bilateral orchiectomy.
The major efficacy outcome was radiographic progression–free survival assessed by blinded independent central review. Overall survival was an additional efficacy outcome. Treatment with darolutamide resulted in a statistically significant improvement in radiographic progression–free survival compared to placebo. Median radiographic progression–free survival was not reached in the darolutamide arm and was 25 months (95% confidence interval [CI] = 19 months to not reached) in the placebo arm (hazard ratio [HR] = 0.54; 95% CI = 0.41–0.71; P < .0001). There was no statistically significant improvement in overall survival at the final analysis (HR = 0.78; 95% CI = 0.58–1.05).
Adverse reactions were consistent with prior experience with darolutamide as a single agent. The darolutamide prescribing information includes warnings and precautions for ischemic heart disease, seizure, and embryo-fetal toxicity.
The recommended darolutamide dose is 600 mg (two 300-mg tablets) taken orally, twice daily, with food until disease progression or unacceptable toxicity.
