FDA approves darolutamide for metastatic castration-sensitive prostate cancer
Regulatory approval: On June 3, 2025, the FDA approved darolutamide (Nubeqa) for metastatic castration-sensitive prostate cancer (mCSPC). Approval was based on the phase 3 ARANOTE trial (n=669), where darolutamide plus ongoing androgen deprivation significantly improved radiographic progression-free survival vs placebo (HR 0.54; p<0.0001); median rPFS was not reached vs 25 months. Overall survival was not statistically significantly improved at final analysis (HR 0.78).
FDA approval (June 3, 2025): darolutamide for mCSPC
The FDA approved darolutamide (Nubeqa; Bayer Healthcare Pharmaceuticals Inc.) on June 3, 2025 for metastatic castration-sensitive prostate cancer (mCSPC). The FDA had previously approved darolutamide in combination with docetaxel for mCSPC.
Evidence base
Efficacy and safety were evaluated in ARANOTE (NCT02799602), a randomized, double-blind, placebo-controlled trial enrolling 669 patients with mCSPC. Patients received darolutamide or placebo; all received a GnRH analog concurrently or had prior bilateral orchiectomy.
- Primary endpoint: radiographic progression-free survival (rPFS) by blinded independent central review
- Key results: rPFS significantly improved with darolutamide vs placebo: HR 0.54 (95% CI, 0.41–0.71; p<0.0001). Median rPFS was not reached with darolutamide vs 25 months with placebo (95% CI, 19–NR).
- Overall survival: no statistically significant improvement at final analysis: HR 0.78 (95% CI, 0.58–1.05).
Safety and dosing
Adverse reactions were described as consistent with prior single-agent experience; labeling includes warnings/precautions for ischemic heart disease, seizure, and embryo-fetal toxicity. Recommended dose: 600 mg orally twice daily with food until progression or unacceptable toxicity.
Regulatory note
Review occurred under Project Orbis; application reviews were ongoing at collaborating agencies outside the FDA at the time of the announcement.