Fizazi K, et al. - In this study, investigators observed a significantly longer metastasis-free survival with darolutamide among people with nonmetastatic, castration-resistant prostate cancer. They also noticed a similar incidence of adverse events for darolutamide and placebo.

Methods

• In this randomized, double-blind, placebo-controlled, phase 3 trial, they included males with nonmetastatic, castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less.
• They randomly assigned the candidates in a 2:1 ratio to receive darolutamide (600 mg [two 300-mg tablets] twice daily) or placebo while continuing androgen-deprivation therapy.
• They considered the primary end point, metastasis-free survival, with the presence of metastasis determined by independent central review of radiographic imaging every 16 weeks.

Results

• A sum of 1509 subjects were randomized ie, 955 to the darolutamide group and 554 to the placebo group.
• The median metastasis-free survival was 40.4 months with darolutamide, as compared with 18.4 months with placebo (hazard ratio for metastasis or death in the darolutamide group, 0.41; 95% confidence interval, 0.34 to 0.50; P < 0.001) in the planned primary analysis performed after 437 primary end-point events had occurred.
• They observed a relation of darolutamide with benefits with respect to all secondary end points, involving overall survival, time to pain progression, time to cytotoxic chemotherapy, and time to a symptomatic skeletal event.
• They noticed similar incidences of adverse events which occurred or worsened during the therapy period and had a frequency of 5% or more or were of grade 3 or higher in the 2 groups; all such events except fatigue were recorded in less than 10% of cases in either group.
• About 8.9% of cases discontinued the assigned regimen because of adverse events in the darolutamide group and 8.7% in the placebo group.
• Darolutamide was not correlated with greater incidence of seizures, falls, fractures, cognitive disorder, or hypertension in comparison with placebo.