Efficacy was based on ARASENS (NCT02799602), a randomized, multicenter, double-blind, placebo-controlled clinical trial in 1306 patients with mHSPC. Patients were randomized to receive either darolutamide 600 mg orally twice daily plus docetaxel 75 mg/m2 intravenously administered every 3 weeks for up to 6 cycles or docetaxel plus placebo. All patients received a gonadotropin-releasing hormone analog concurrently or had a bilateral orchiectomy.
The primary efficacy measure was overall survival (OS). Time-to-pain progression was an additional efficacy measure. Median OS was not reached (NR) (95% CI: NR, NR) in the darolutamide plus docetaxel arm and 48.9 months (95% CI: 44.4, NR) in docetaxel plus placebo arm (HR 0.68; 95% CI: 0.57, 0.80; p<0.0001). Treatment with darolutamide and docetaxel resulted in a statistically significant delay in time-to-pain progression (HR 0.79; 95% CI: 0.66, 0.95; 1-sided p=0.006).
The median age of patients was 67 years (41 to 89) and 17% were 75 years or older. Selected demographics were reported as follows: 52% White, 36% Asian, 4% Black or African American, 7% Hispanic/Latino. Three percent of patients had M1a disease (spread to distant lymph nodes), 83% had M1b (spread to bones), and 14% had M1c (spread to organs).
The most common adverse reactions experienced by patients (incidence ≥10% with a ≥2% increase over placebo with docetaxel) were constipation, decreased appetite, rash, hemorrhage, increased weight, and hypertension. The most common laboratory test abnormalities (≥30%) were anemia, hyperglycemia, decreased lymphocyte count, decreased neutrophil count, increased AST, increased ALT, and hypocalcemia.
The recommended darolutamide dose for mHSPC is 600 mg (two 300 mg tablets) taken orally, twice daily, with food until unacceptable toxicity or disease progression. Docetaxel, 75 mg/m2 intravenously is administered every 3 weeks for up to 6 cycles. The first dose of docetaxel should be administered within 6 weeks after the start of darolutamide treatment.
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Source: "FDA Approves Darolutamide Tablets For Metastatic Hormone-Sensitive Pro". 2022. U.S. Food And Drug Administration.
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