(UroToday.com) The 2023 American Society of Clinical Oncology (ASCO) annual meeting included a prostate cancer session featuring a presentation by Dr. Alicia Morgans discussing DEAR, a comparative real-world evidence study of darolutamide, enzalutamide, and apalutamide for patients with nmCRPC in the United States. Novel androgen receptor inhibitors (ARIs) are recommended for patients with nmCRPC. Darolutamide has a distinct structure with low blood-brain barrier penetration which may lead to a lower risk of central nervous system-related adverse events and minimal risk of adverse events commonly associated with ARIs.1 There is limited real-world evidence on ARI discontinuations, the underlying reasons for discontinuation, the incidence of adverse events, and disease progression for different ARIs. DEAR is the first study comparing real-world utilization, outcomes, and adverse events between darolutamide and enzalutamide/apalutamide in nmCRPC patients.
This retrospective chart review cohort study uses electronic medical records from the PPS network of US urology practices. Eligible patients had nmCRPC, no prior novel hormonal therapy, and initiated first ARI treatment (index date) between August 1, 2019 and March 31, 2022:
Dr. Morgans and colleagues describe the percentage of patients who discontinued initial ARI treatment, percentage who progressed to metastasis, and percentage with adverse events. A comparative analysis was performed between darolutamide and enzalutamide/apalutamide using Cox proportional hazards models for time to discontinued initial ARI treatment/time to percentage who progressed to metastasis, adjusting for observed baseline factors.
There were 870 patients included in the study, including 362 that received darolutamide, 382 receiving enzalutamide, and 126 receiving apalutamide. The median age (80/79/80 years), median baseline PSA doubling time (6.8/6.4/7.4 months), baseline characteristics, and median follow-up (22.2/22.7/23.3 months) were similar for darolutamide/enzalutamide/apalutamide:
A lower percentage of patients had discontinued initial ARI treatment event on darolutamide vs enzalutamide/apalutamide (30.4% vs 40.8%/46.0%):
The proportion of patients who progressed to metastasis event was also lower for darolutamide (17.7% vs 28.3%/27.8%) during the study period:
Multivariate analyses adjusting for baseline factors showed that patients on darolutamide had a lower risk of discontinued initial ARI treatment:
and percentage who progressed to metastasis over time vs enzalutamide/apalutamide:
A lower percentage of patients on darolutamide had adverse events vs enzalutamide/apalutamide (24.9 vs 29.3/30.2):
The most common reason for nmCRPC treatment discontinuation was occurrence of adverse events (darolutamide 10.2%, enzalutamide 14.4%, apalutamide 15.1%):
Dr. Morgans concluded her presentation discussing DEAR, a comparative real-world evidence study of darolutamide, enzalutamide, and apalutamide for patients with nmCRPC in the United States with the following take-home points:
- Overall, a lower percentage of patients discontinued initial ARI treatment, progressed to metastasis, or had adverse events on darolutamide vs enzalutamide/apalutamide
- In analyses adjusting for observed baseline factors, patients on darolutamide had considerably lower risk of discontinued initial ARI treatment and a percentage who progressed to metastasis vs enzalutamide/apalutamide
- This study confirms darolutamide’s strong efficacy and favorable tolerability profile in a real-world setting
- The longer treatment duration seen with darolutamide may be associated with a lower risk of progression to mCRPC vs enzalutamide/apalutamide
- Future studies are needed to confirm these results in other populations or using other data sources
Presented by: Alicia K. Morgans, MD, MPH, GU Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.
References: