EAU 2021: Hormone Treatment–related Adverse Events (HTR AEs) with Darolutamide (DARO) in Patients (Pts) with Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC) from the Phase 3 ARAMIS Study

(UroToday.com) Darolutamide (DARO) is a structurally distinct androgen receptor inhibitor (ARI) that has been demonstrated to significantly prolong metastasis-free survival and overall survival in the ARAMIS trial.1

Men with nmCRPC are generally asymptomatic from their cancer, but they may experience cancer treatment-related AEs that can affect daily life. DARO has a consistently favorable safety profile. In the final analysis of ARAMIS (15 Nov 2019), discontinuation rates due to AEs and the incidence of most AEs commonly associated with ARI therapy were similar for DARO and placebo (PBO). Hormone treatment-related (HTR) AEs include hot flush, gynecomastia, osteoporosis, erectile dysfunction, anemia, diabetes, cardiac disorders, weight gain, memory impairment, dyslipidemia, fatigue, hypertension, falls, and fractures.

In this abstract, the authors present HTR AEs for DARO treatment and characterize their onset and occurrence over time versus PBO. HTR AE rates were determined by Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Time interval-specific new and cumulative event rates of HTR AEs were analyzed during the double-blind (DB) period. Osteoporosis was not objectively measured in ARAMIS and is not included in this analysis. Event rates for erectile dysfunction, memory impairment, diabetes, acute myocardial infarction, heart failure, weight gain, and dyslipidemia were too low (≤2%) to provide meaningful time interval-specific analyses. The observation period included time intervals with ≥10% of the population at risk in each cohort. Each site’s ethics committee approved the study.

Median treatment durations were 18.5 months for DARO and 11.6 months for PBO during the DB period. DARO showed ≤2% difference compared with PBO for HTR AEs of hot flush, gynecomastia, anemia, coronary artery disorders, hypertension, falls, and fractures.

Cumulative Incidence of all AE’s shown below:


Fatigue was the only AE with a >10% incidence in the DARO arm (13.2% vs 8.3% in PBO arm). Hot flush and fatigue had an early onset, with most new events occurring during the first month of DARO treatment. Anemia increased during the first 6 months and then decreased after 1 year. New onset of gynecomastia, coronary artery disorders, and hypertension was not time specific for DARO or PBO. Falls and fractures had a later onset.

Looking specifically at fatigure:


The cumulative incidence stabilizes over time and most new events were within the first month of treatment.

Cumulative event rates were similar between DARO and PBO for HTR AEs, except fatigue, and showed minimal increase over time.

Based on this analysis, the authors conclude that, consistent with previous safety reports, DARO was well tolerated in patients with nmCRPC. Most HTR AEs occurred at a low incidence with DARO and with similar incidence to that of PBO. HTR AEs showed minimal increase with continued treatment.

Presented by: Karim Fizazi, MD, PhD, Gustave Roussy, University of Paris-Saclay in Villejuif, France.

Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Assistant Professor of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, @tchandra_uromd on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.


  1. Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, Le Berre MA, Petrenciuc O, Snapir A, Sarapohja T, Smith MR; ARAMIS Investigators. Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. N Engl J Med. 2020 Sep 10;383(11):1040-1049. doi: 10.1056/NEJMoa2001342. PMID: 32905676.