Darolutamide increases survival in patients with metastatic, hormone-sensitive prostate cancer: NEJM
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.
