(UroToday.com) In a moderated poster presentation at the 2022 American Urologic Association Annual Meeting held in New Orleans and virtually, Dr. Cicone provided an analysis reporting real world adverse event results with the use of darolutamide. Darolutamide, an oral androgen receptor inhibitor, has been approved for the treatment of patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). This approval was based on significant improvements in metastasis-free survival (MFS) in the ARAMIS clinical trial. Further, ongoing follow-up of the ARAMIS cohort demonstrated improvements in overall survival with favourable toxicity profile. However, the authors sought to examine adverse events (AEs) associated with darolutamide treatment using real life data from EudraVigilance (EV) and the FAERS databases.
The authors used the EV database in European Economic Area and the FAERS database in the United States to identify darolutamide-related AEs occurring from July 30, 2019 and October 1, 2021. Each AE was characterized with respect to category and severity. These results were subsequently compared to the toxicity results of the ARAMIS trial. In the context of the EV dataset, the authors further examined the modifying effect of patient age (categorized as more or less than 85 years). They used pooled relative risk (PRR) to compare groups.
In the EV database, 139 AEs related to darolutamide were identified, of which 54 (39%) were serious and 2 (0.01%) were deaths. In the FDA FAERS database, 257 adverse events related to darolutamide were reported with 137 (53%) serious events and 8 (3%) deaths. In the ARAMIS registry study, 794 AEs were reported, with serious AEs occurring in 24.8% of patients receiving darolutamide, with 1 death related to trial regimen.
Fatigue was the most common AE reported in all three datasets, respectively 115 events (12.1%) in the ARAMIS registry, 33 events (12.8%) in FDA-FAERS and 13 events (9.3%) in EV. However, no significant differences were found across all three datasets in terms of fatigue, diarrhea and nausea (PRR 0.80 – 1.50) (p >0.05). Interestingly, in the ARAMIS registry, rates of back pain, arthralgia, hypertension, constipation, pain in an extremity, anemia, hot flush, UTIs and urinary retention were found compared to EV and FDA-FAERS databases (PRR 1.50-7.00, p <0.05). Unfortunately, the EV dataset is unable to provide a denominator of the number of patients receiving therapy.
The authors conclude that these data demonstrate that darolutamide is safe and relatively well tolerated in real world practice. The most frequent side effect is fatigue.
Presented by: Antonio Cicione, MD, Rome, Italy