Background
Men with nonmetastatic castration-resistant prostate cancer (nmCRPC) are generally asymptomatic and may receive prolonged treatment with androgen receptor inhibitors (ARIs). Understanding the burden and time course of adverse events (AEs) commonly associated with ARIs that may impact patients’ daily life will help inform optimal treatment selection for men with nmCRPC. We present analyses of time to AEs of interest associated with some ARIs (fatigue, falls, fracture, hypertension, mental impairment, and rash) and the cumulative incidence of these AEs, grade 3/4 AEs, and serious AEs from ARAMIS.
Methods
Men with nmCRPC were randomized 2:1 to darolutamide (DARO; n=955) or placebo (PBO; n=554) while continuing androgen deprivation therapy. The cumulative incidence of AEs was analyzed using Kaplan-Meier estimates for the first 24 months of the double-blind (DB) period to ensure >10% of the population in each treatment cohort. Time interval–specific analysis determined new event rates at each scheduled study visit.
Results
During the first 24 months of the DB period, the incidence of AEs of interest in the DARO group was low and ≤2% different from that in the PBO group, except for fatigue. During the first month of DARO and PBO treatment, new event rates were very low and similar for falls (0.2%, 0.7%), fractures (0.4%, 0.5%), mental impairment (0%, 0.4%), hypertension (1.7%, 1.1%), and rash (0.7%, 0.2%). In men who had fatigue during the first 24 months (DARO, 12.6% and PBO, 8.3%), almost half of the men experienced fatigue onset during the first month in both arms (DARO, 5.9% vs PBO, 4.0%). The cumulative incidence of rash was 2.9% (PBO 1.1%) at 24 months, with half of the events occurring in the first 4 months and almost all being grade 1 or 2. The rate of initial onset and cumulative incidence of grade 3/4 AEs and serious AEs were similar for DARO and PBO groups over 24 months.
Conclusions
The time course profile of most AEs of interest, grade 3/4 AEs, and serious AEs confirms the safety profile of DARO, showing a similar onset and cumulative incidence versus PBO. Most events of fatigue were reported early in treatment, and the incidence of rash was very low, with almost all being grade 1 or 2 events.
Clinical trial identification
NCT02200614.