Clinical Pearls & Morning Reports
Published September 9, 2020
In the planned primary analysis of this phase 3 trial evaluating darolutamide in men with nonmetastatic, castration-resistant prostate cancer, the median metastasis-free survival was significantly longer with darolutamide (40.4 months) than with placebo (18.4 months). Fizazi et al. recently published the results of a prespecified final analysis of overall survival and other outcomes of that trial. Read the NEJM Original Article here.
Q: What is darolutamide?
A: Darolutamide is a structurally distinct androgen-receptor inhibitor, and is approved for the treatment of nonmetastatic, castration-resistant prostate cancer on the basis of the current trial — the phase 3 Androgen Receptor Antagonizing Agent for Metastasis-free Survival (ARAMIS) trial.
Q: Was darolutamide associated with an overall survival benefit, as compared with placebo, in the final analysis of the trial by Fizazi et al.?
A: Overall survival at 3 years was 83% (95% confidence interval [CI], 80 to 86) in the darolutamide group and 77% (95% CI, 72 to 81) in the placebo group. The risk of death was significantly lower, by 31%, in the darolutamide group than in the placebo group (hazard ratio for death, 0.69; 95% CI, 0.53 to 0.88; P=0.003). This overall survival benefit was observed despite the fact that more than half the patients in the placebo group (307 of the 554 patients) received subsequent treatment with darolutamide or other life-prolonging therapy.
A: As compared with placebo, treatment with darolutamide resulted in a significantly longer time to first use of cytotoxic chemotherapy, a significantly longer time to first symptomatic skeletal event, and a significantly longer time to pain progression.
A: The results of the final analysis of the safety profile of darolutamide are consistent with those of the primary analysis reported previously. Fatigue was reported in 13.2% of the patients in the darolutamide group and was the only adverse event reported in more than 10% of the patients in that group during the double-blind period. The incidence of all other adverse events that occurred in more than 5% of the patients in either group was generally similar in the two groups. The incidence of adverse events commonly associated with androgen-receptor inhibitors, including falls, seizures, mental-impairment disorders, and hypertension, was similar in the two groups. The incidence of fractures was slightly higher in the darolutamide group than in the placebo group; however, after adjustment for the duration of exposure, the between-group difference decreased.