Presenting Author: Kirollos Hanna, PharmD, BCPS, BCOP, FACCC, Mayo Clinic College of Medicine, St. Paul, MN
Co-Authors: Alicia K. Morgans, MD, Dana-Farber Cancer Institute, Boston, MA; Neal D. Shore, MD, Carolina Urologic Research Center, Myrtle Beach, SC; Nasreen Khan, PhD, Bayer HealthCare, Whippany, NJ; Niculae Constantinovici, MD, Bayer Consumer Care AG, Basel, Switzerland; Javeed Khan, MSc, Bayer UK, Reading, England; Guifang Chen, MSc, Bayer HealthCare, Whippany, NJ; Julie Xu, MSc, Bayer Canada, Mississauga, ON, Canada; Jorge Ortiz, MD, Bayer HealthCare, Whippany, NJ; Daniel J George, MD, Duke Cancer Institute, Durham, NC
BACKGROUND: Androgen receptor inhibitors (ARIs) are recommended for patients with nonmetastatic, castration-resistant prostate cancer (nmCRPC). Darolutamide, a novel ARI, has a distinct structure with low blood-brain barrier penetration which may confer a lower risk for central nervous system–related adverse events (AEs), and a lower risk for the AEs that are frequently associated with ARIs.
OBJECTIVE: DEAR (NCT05362149) is the first study comparing the real-world utilization, outcomes, and AEs of darolutamide versus enzalutamide and apalutamide in patients with nmCRPC.
METHODS: DEAR was a retrospective chart review cohort study that used electronic medical records from the Precision Point Specialty network of US urology practices. Eligible patients had nmCRPC, no previous novel hormonal therapy, and had initiated their first ARI treatment (index date) between August 2019 and March 2022. The outcomes analyzed included the proportion of patients who discontinued initial ARI treatment and the reasons for ARI discontinuation, the proportion whose disease progressed to metastatic CRPC (mCRPC), and the incidence of AEs. A comparative analysis was performed of the patients who received darolutamide versus those who received enzalutamide and those who received apalutamide using the Cox proportional hazards model for the time to discontinuation and time to mCRPC, adjusting for observed baseline factors.
RESULTS: In total, 870 patients were included (darolutamide n=362; enzalutamide n=382; apalutamide n=126). The median ages were 80, 79, and 80 years; the median baseline prostate-specific antigen doubling times were 6.8 months, 6.4, months, and 7.4 months; and the median follow-up times were 22.2 months, 22.7 months, and 23.3 months for darolutamide, enzalutamide, and apalutamide, respectively. Other baseline characteristics were similar across all groups. A lower proportion of patients discontinued darolutamide versus enzalutamide or apalutamide (30.4% vs 40.8% and 46%) or an mCRPC event (17.7% vs 28.3% and 27.8%) during the study period. The most common reason for treatment discontinuation was for AEs (darolutamide, 10.2%; enzalutamide, 14.4%; apalutamide, 15.1%). Multivariate analyses adjusting for baseline factors showed that patients who received darolutamide had a lower risk for ARI discontinuation (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.56-0.94 vs HR, 0.61; 95% CI, 0.44-0.85;) and mCRPC (HR, 0.59; 95% CI, 0.43-0.82 vs HR, 0.65; 95% CI, 0.42-0.99) over time versus enzalutamide and apalutamide. A lower proportion of patients receiving darolutamide had AEs versus enzalutamide and apalutamide (24.9% vs 29.3% and 30.2%).
CONCLUSION: Overall, a lower proportion of patients discontinued their initial ARI treatment, had disease progression to mCRPC, or had AEs after receiving darolutamide versus enzalutamide or apalutamide. In analyses adjusting for observed baseline factors, the patients who received darolutamide had a considerably lower risks for ARI discontinuation and mCRPC than the patients who received enzalutamide or apalutamide. This study confirms the efficacy and favorable tolerability profile of darolutamide in a real-world setting.
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