USA: Findings from a trial showed that the addition of darolutamide to androgen-deprivation therapy, and docetaxel increased overall survival in patients with hormone-sensitive prostate cancer. The frequency of adverse events however was found to be similar in both the groups -- the darolutamide group (darolutamide, androgen-deprivation therapy, and docetaxel) versus the placebo group (placebo plus androgen-deprivation therapy and docetaxel).

Darolutamide is a potent androgen-receptor inhibitor that has shown to be associated with increased overall survival in patients with nonmetastatic, castration-resistant prostate cancer. Matthew R. Smith and colleagues in their study published in the New England Journal of Medicine aimed to determine whether a combo of darolutamide, androgen-deprivation therapy, and docetaxel would increase survival among patients with metastatic, hormone-sensitive prostate cancer.
The international, phase 3 trial included 1306 patients with metastatic, hormone-sensitive prostate cancer. They were randomly assigned in the ratio of 1:1 to receive darolutamide (at a dose of 600 mg [two 300-mg tablets] twice daily; n=651) or matching placebo (n=655), both in combination with androgen-deprivation therapy and docetaxel. The primary endpoint was overall survival.
The study revealed the following findings:
86.1% of the patients had a disease that was metastatic at the time of the initial diagnosis.
At the data cutoff date for the primary analysis (October 25, 2021), the risk of death was significantly lower, by 32.5%, in the darolutamide group than in the placebo group (hazard ratio 0.68).
Darolutamide was also associated with consistent benefits with respect to the secondary endpoints and prespecified subgroups.
Adverse events were similar in the two groups, and the incidences of the most common adverse events (occurring in ≥10% of the patients) were highest during the overlapping docetaxel treatment period in both groups.
The frequency of grade 3 or 4 adverse events was 66.1% in the darolutamide group and 63.5% in the placebo group; neutropenia was the most common grade 3 or 4 adverse event (in 33.7% and 34.2%, respectively).
To conclude, patients in the darolutamide versus placebo group had a significantly longer overall survival, and the addition of darolutamide led to improvement in key secondary endpoints. The frequency of adverse events was similar in the two groups.
Reference:
The study titled, "Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer," was published in the New England Journal of Medicine.
DOI: 10.1056/NEJMoa2119115