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Darolutamide safety analysis supports its use in patients with nmCRPC


A safety analysis of darolutamide (Nubeqa) from the pivotal phase 3 ARAMIS shared during the 2021 ESMO Congress provides valuable information on optimizing the use of the androgen receptor antagonist in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC).1

The findings showed that in men with nmCRPC, darolutamide had a similar safety profile as placebo, with comparable rates of adverse event (AE) onset and occurrence. In the ARAMIS trial (NCT02200614), there was a ≤2% difference in AE incidence of interest between the experimental and placebo group, and severity was low for both arms across 24 months. Fatigue was the only exception, with 12.6% of the darolutamide group who experienced the AE.

Notably, the incidence of rash was very low and nearly all cases of fatigue were reported early on in treatment. Most events were grade 1 or 2. The investigators noted that darolutamide poses a particular significance to the overall wellbeing of men with nmCRPC, given their potentially prolonged treatment time.

Dr. Christian Gratzke, professor and chair in the Department of Urology at the Albert-Ludwigs-University in Freiburg, Germany

Christian Gratzke, MD

“Men with nonmetastatic castration-resistant prostate cancer are generally asymptomatic and may receive prolonged treatment with androgen receptor inhibitors (ARIs),” Christian Gratzke, MD, professor and chair in the Department of Urology at the Albert-Ludwigs-University in Freiburg, Germany, explained in a corresponding abstract presented alongside the poster. “Understanding the burden and time course of adverse events commonly associated with ARIs that may impact patients’ daily life will help inform optimal treatment selection for men with nmCRPC.”

Researchers analyzed the AEs most associated with antigen receptor inhibitors to provide patients with optimal treatment selection information. Kaplan-Meier estimates were utilized to analyze the incidence of AEs across the first 24 months. Time interval-specific analysis determined new event rates per each scheduled study visit.

Participants were randomized 2:1 to either receive darolutamide or placebo while continuing treatment with androgen deprivation therapy. The darolutamide group included 995 men, while the placebo group included 554.

Observed AEs across the darolutamide and placebo arms, respectively, included falls (0.2% vs 0.7%), fractures (0.4% vs 0.5%), mental impairment (0% vs 0.4%), hypertension (1.7% vs 1.1%), and rash (0.7% vs 0.2%).

Fatigue was reported by 12.6% of the men who received darolutamide, and by 8.3% of the placebo arm. Nearly half of all men who reported fatigue experienced it during the first month (5.9% vs 4.0%, respectively). The total rash incidences was 2.9% by 24 months. Half of all reported cases of rash appeared in the first 4 months, and almost all were grade 1 or 2. Serious AE incidence and initial onset were similar between the 2 groups.

Fatigue was shown to increase in cumulative incidence over time. In comparison, falls and fractures were mostly reported in the first month of treatment.

Hypertension onset was not specific to time interval. The number of cumulative incidences reported were similar across treatments. Although mental impairment was rare (<1% per treatment group), incidence occurrence was consistent across both groups.

While most cases of rash were grade 1 or 2, there were 2 patients who reported a grade 3 rash from the darolutamide group, and 1 patient who reported a grade 3 rash from the placebo group.

“The findings from this analysis confirm the safety profile of darolutamide showing a low incidence in a similar onset and cumulative incidence versus placebo,” Gratzke concluded.


1. Gratzke CJ, Fizazi K, Shore ND, et al. Time course profile of adverse events of interest and serious adverse events with darolutamide in the ARAMIS trial. Presented at: 2021 European Society Medical Oncology Congress; September 16-21, 2021’ Virtual. Abstract 630P.

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