Darolutamide improves OS in nmCRPC

Treatment with darolutamide significantly improved overall survival (OS) in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), according to a prespecified final analysis of the ARAMIS* study presented at ESMO Asia 2020.

This phase III, multicentre, double-blind trial involved 1,509 patients with nmCRPC who were randomized in a 2:1 ratio to receive either darolutamide 600 mg twice daily (n=955) or placebo (n=554) in addition to androgen deprivation therapy (ADT). After unblinding, 170 patients in the placebo group crossed over to receive open-label darolutamide. [ESMO Asia 2020, abstract 740; N Engl J Med 2020;383:1040-1049]

At 3 years, the OS rate was higher in the darolutamide arm, with a 31 percent significant reduction in the risk of death, compared with the placebo arm (83 percent vs 77 percent; hazard ratio [HR], 0.69; p=0.003).

“The OS benefit was observed despite more than half of the patients in the placebo group receiving subsequent darolutamide or other life-prolonging therapy (docetaxel, abiraterone/abiraterone acetate, enzalutamide, sipuleucel-T, and cabazitaxel),” said lead author Dr Karim Fizazi from Institut Gustave Roussy and University of Paris-Saclay in Villejuif, France.

Darolutamide-treated patients also had significantly longer time to pain progression (median 40.3 vs 25.4 months; HR, 0.65; p<0.001), time to first use of cytotoxic chemotherapy (HR, 0.58; p<0.001), and time to first symptomatic skeletal event (HR, 0.48; p=0.005) at 3 years compared with placebo-treated patients.

Time to first prostate cancer-related invasive procedure (HR, 0.42; p<0.001) and time to initiation of subsequent antineoplastic therapy (HR, 0.36; p<0.001) were also significantly longer with darolutamide compared with placebo.

The incidence of treatment-emergent adverse events (AEs) was similar between the darolutamide and placebo arms (85.7 percent vs 79.2 percent). “With [this] extended follow-up, the safety profile of darolutamide was favourable and consistent with the primary analysis [that has been] previously reported. [Also,] incidences of most ARI**-associated AEs were not increased with darolutamide vs placebo, taking treatment exposure into account,” Fizazi said.

“[In conclusion,] darolutamide significantly improved OS vs placebo in men with nmCRPC, regardless of the effect of crossover (31 percent of men in the placebo group) and subsequent therapies ... [The study drug also] significantly delayed the onset of cancer-associated morbidity and subsequent chemotherapy,” noted Fizazi.

“These results provide further compelling evidence for early darolutamide treatment in men with nmCRPC,” he added.

*ARAMIS: Efficacy and safety study of darolutamide (ODM-201) in men with high-risk nonmetastatic castration-resistant prostate cancer

**ARI: Androgen receptor inhibitor