Among the novel androgen receptor inhibitors (ARIs), darolutamide has slight advantages over enzalutamide and apalutamide for men with nonmetastatic castration-resistant prostate cancer (nmCRPC) in real-world practice. Results of the DEAR study were presented at the American Society of Clinical Oncology’s 2023 annual meeting.

Using electronic medical records from the Precision Point Specialty network of US urology practices, investigators identified 362 patients initiating darolutamide, 382 initiating enzalutamide, and 126 initiating apalutamide. The median baseline PSA doubling time was similar between groups: 6.8, 6.4, and 7.4 months for darolutamide, enzalutamide, and apalutamide, respectively. The median age was 79-80 years.

A lower proportion of patients taking darolutamide (30.4%) discontinued their ARI drug compared with the enzalutamide group (40.8%) and apalutamide group (46.0%). In an adjusted Cox proportional hazards model, darolutamide users had a significant 27% and 39% lower risk of discontinuation compared with enzalutamide and apalutamide users, respectively, Alicia K. Morgans, MD, MPH, of Dana-Farber Cancer Institute in Boston, Massachusetts, and colleagues reported.

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The proportion of patients progressing to metastatic disease was also lower with darolutamide: 17.7% of these patients progressed compared with 28.3% of enzalutamide and 27.8% of apalutamide users during a median 2 years of follow-up. Darolutamide users had a significant 41% and 35% lower risk of progression compared with enzalutamide and apalutamide users, respectively, the investigators reported.

A numerically lower proportion of patients on darolutamide had adverse events: 24.9% vs 29.3% and 30.2%, respectively. Dr Morgans’ team noted that darolutamide has low blood-brain barrier penetration which may lead to a lower risk of central nervous system-related adverse events, such as seizures and falls, and minimal risk of other adverse events commonly associated with ARIs.

“This study confirms [darolutamide]’s strong efficacy and favorable tolerability profile in a [real-world] setting,” the investigators concluded in a study abstract. “The longer treatment duration seen with [darolutamide] may be associated with a lower risk of progression to mCRPC vs [enzalutamide/apalutamide].”

Disclosure: This research was supported by Bayer AG. Please see the original reference for a full list of disclosures.


Morgans AK, Shore ND, Khan N, et al. Comparative real-world (RW) evidence on darolutamide (Daro), enzalutamide (Enza), and apalutamide (Apa) for patients (Pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) in the United States: DEAR. J Clin Oncol 41(16):5097-5097. doi:10.1200/JCO.2023.41.16_suppl.5097