Treatment of Nonmetastatic Castration-Resistant Prostate Cancer With Darolutamide

[Balsam01]

TAKE-HOME MESSAGE

The results of this placebo-controlled randomized trial show that darolutamide was associated with improved overall survival at 3 years compared with placebo (83% vs 77%) and a reduced hazard for death (HR, 0.69) among patients with nonmetastatic castration-resistant prostate cancer treated with concurrent androgen-deprivation therapy.

Darolutamide is associated with a survival benefit without significant toxicity concerns in this patient population.

– Neil Majithia, MD

BACKGROUND

Darolutamide is a structurally distinct androgen-receptor inhibitor that is approved for the treatment of nonmetastatic, castration-resistant prostate cancer. In the planned primary analysis of a phase 3 trial, the median metastasis-free survival was significantly longer with darolutamide (40.4 months) than with placebo (18.4 months). The data for the analysis of overall survival were immature at the time of the primary analysis.

METHODS

In this double-blind, placebo-controlled trial, we randomly assigned 1509 men, in a 2:1 ratio, to receive darolutamide (955 patients) or placebo (554 patients) while they continued to receive androgen-deprivation therapy. After the results of the primary end-point analysis were found to be positive, unblinding of the treatment assignments occurred, 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 end points were evaluated.

RESULTS

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. 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). Darolutamide was also associated with a significant benefit with respect to all other secondary end points, including the time to first symptomatic skeletal event and the time to 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.

CONCLUSIONS

Among men with nonmetastatic, castration-resistant prostate cancer, the percentage of patients who were alive at 3 years was significantly higher among those who received darolutamide than among those who received placebo. The incidence of adverse events was similar in the two groups.

CITATION

The New England Journal of Medicine

Nonmetastatic Castration-Resistant Prostate Cancer and Survival With Darolutamide

N. Engl. J. Med 2020 Sep 10;383(11)1040-1049, K Fizazi, N Shore, TL Tammela, A Ulys

[j-o-h-n]

Just to let you know..... we all didn't suddenly go blind....

Good Luck, Good Health and Good Humor.

j-o-h-n Friday 09/18/2020 7:10 PM DST

[BruceSF]

So do these results mean the FDA will soon approve darolutamide for hormone sensitive metastatic PCa? It seems to have fewer side effects than enzutamide or apalutamide (and probably abiraterone+prednisone), so if it’s equally effective it should become the new choice (combined with ADT) for de novo metastatic patients.