Darolutamide improves survival in nonmetastatic prostate cancer patients: NEJM
Delhi: The administration of Darolutamide in men with nonmetastatic, castration-resistant prostate cancer led to a significantly higher rate of survival, according to results from ARAMIS trial in the New England Journal of Medicine.
Darolutamide, a structurally distinct androgen-receptor inhibitor, is approved for the treatment of nonmetastatic, castration-resistant prostate cancer. Findings from the planned primary analysis of a phase 3 trial showed significantly higher median metastasis-free survival with Darolutamide (40.4 months) than with placebo (18.4 months). However, the primary analysis data lacked the data for the analysis of overall survival.
To fill this knowledge gap, Karim Fizazi, head of the department of cancer medicine at Institut Gustave Roussy in Villejuif, France, and colleagues performed a double-blind, placebo-controlled trial. In the trial,1509 men were assigned in the ratio 2:1 to receive darolutamide (955 patients) or placebo (554 patients). They continued to receive androgen-deprivation therapy. They were followed for a median of 29.0 months.
Unblinding of the treatment assignments occurred, after the results of the primary end-point analysis were found to be positive, and patients in the placebo group were permitted to cross over to receive open-label darolutamide treatment. At the time of this prespecified final analysis, which had been planned to be performed after approximately 240 deaths had occurred, overall survival and all other secondary endpoints were evaluated.
The median follow-up time was 29.0 months. At the time of unblinding of the data, all 170 patients who were still receiving placebo crossed over to receive darolutamide; 137 patients who had discontinued placebo before unblinding had occurred received at least one other life-prolonging therapy.
Key findings of the study include:
- Overall survival at 3 years was 83% in the darolutamide group and 77% 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).
- Darolutamide was also associated with a significant benefit with respect to all other secondary endpoints, including the time to the first symptomatic skeletal event and the time to the first use of cytotoxic chemotherapy.
- The incidence of adverse events after the start of treatment was similar in the two groups; no new safety signals were observed.
"The percentage of patients who were alive at 3 years was significantly higher in men with nonmetastatic, castration-resistant prostate cancer who received darolutamide than among those who received a placebo. The incidence of adverse events was similar in the two groups," concluded the authors.
The study, "Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide," is published in the New England Journal of Medicine.