On July 30, 2019, the FDA approved darolutamide (Nubeqa; Bayer) for the treatment of patients with nonmetastatic castration-resistant prostate cancer.
This approval was based on the phase 3, double-blind, multicenter, ARAMIS clinical trial of 1509 patients with nonmetastatic castration-resistant prostate cancer. The patients were randomized in a 2:1 ratio to oral darolutamide 600 mg twice daily or placebo until disease progression, unacceptable toxicity, or withdrawal of patient consent. All patients in the trial also continued on androgen-deprivation therapy (ADT). The primary end point was metastasis-free survival (MFS), defined as the time from randomization to first evidence of distant metastasis or death from any cause within 33 weeks after the last evaluable scan, whichever occurred first.
The median MFS was significantly longer in the darolutamide plus ADT arm (40.4 months) compared with the placebo plus ADT arm (18.4 months; P <.0001).
Adverse reactions occurring more frequently with darolutamide (≥2% over placebo) were fatigue (16% vs 11%), extremity pain (6% vs 3%), and rash (3% vs 1%). Adverse reactions leading to treatment discontinuation occurred in 9% of patients in both arms of the clinical trial.