Darolutamide Receives FDA Approval for mCSPC
The FDA approved darolutamide monotherapy for use in metastatic hormone-sensitive prostate cancer following ARANOTE findings. Darolutamide was previously approved in combination with docetaxel for mHSPC. The FDA has granted approval to darolutamide (Nubeqa) for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC), according to an announcement from the regulatory agency.
The efficacy of darolutamide in mHSPC was established by data from the phase 3, randomized, double-blind ARANOTE (NCT02799602) trial. Investigators randomly assigned 669 patients to receive 600 mg of darolutamide, via two 300-mg tablets, twice daily with food, or placebo.
Additionally, all patients either received standard gonadotropin-releasing androgen deprivation therapy (ADT) or had previously received bilateral orchiectomy.
ARANOTE’s primary end point was radiographic progression-free survival (rPFS), as assessed by blinded independent central review, with overall survival (OS) as a secondary end point.
Treatment with darolutamide achieved a 46% reduction in risk of radiographically confirmed progression or death. Researchers identified no statistically significant increase of OS at the final analysis (HR, 0.78; 95% CI, 0.58-1.05).
Patients in the darolutamide arm experienced a statistically significant improvement in rPFS vs the placebo arm and did not reach median rPFS. The placebo arm’s median rPFS was 25 months (95% CI, 19-NR; hazard ratio [HR], 0.54; 95% CI, 0.41-0.71; P < 0.0001).
The FDA recommends a dosage of 600 mg of darolutamide taken twice orally daily with food until disease progression or unacceptable toxicity. The FDA’s announcement also notes that darolutamide’s prescribing information includes warnings for ischemic heart disease, seizure, and embryo-fetal toxicity; in addition, the safety profile of darolutamide reported at the final analysis was consistent with previous findings for darolutamide monotherapy.
The FDA accepted a supplemental new drug application (sNDA) for darolutamide with ADT on November 21 2024. The sNDA was based on prior data from ARANOTE presented at the 2024 ESMO Congress.
Data presented at that time was similar, including a 24-month rPFS rate of 70.3% for patients in the experimental arm and 52.1% for patients receiving placebo.
It was reported at that time that the most common treatment-emergent adverse events (TEAEs) associated with darolutamide were fatigue (5.6%), mental impairment disorder (1.6%), hypertension (9.4%), cardiac arrhythmias (8.8%), coronary artery disorders (3.6%), heart failure (0.9%), falls (1.3%), bone fracture (4.0%), vasodilatation and flushing (9.2%), diabetes mellitus and hyperglycemia (9.0%), and rash (4.3%).
Darolutamide was approved in combination with docetaxel for use in mHSPC on August 22, 2022, based on data from the ARASENS trial (NCT02799602).
