Which ARPI first in chemotherapy-naïve mCRPC? Enzalutamide versus abiraterone: A nationwide real-world study
Jin Bong Choi, Yun-Hee Lee, U-Syn HaBackground
Abiraterone and enzalutamide are widely used androgen receptor pathway inhibitors (ARPIs) for chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC), but the optimal initial treatment strategy remains uncertain, particularly in older and medically complex patients.
Objectives
To compare survival outcomes between enzalutamide-first and abiraterone-first treatment strategies in chemotherapy-naïve patients with mCRPC and to evaluate whether treatment effects differ according to age and comorbidity burden.
Design
Nationwide population-based retrospective cohort study.
Methods
Using the Korean National Health Insurance Service database, we identified chemotherapy-naïve patients with mCRPC who initiated abiraterone or enzalutamide between 2019 and 2020. Patients were classified according to the first ARPI initiated (enzalutamide-first strategy [E+EA] vs abiraterone-first strategy [A+AE]). Propensity score matching based on age and Charlson Comorbidity Index was performed. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS), with subgroup analyses according to age and comorbidity burden.
Results
Among 1,401 patients, 753 initiated enzalutamide and 648 initiated abiraterone. After matching, 648 patients remained in each cohort. Abiraterone-first strategy was associated with worse OS (hazard ratio [HR] 1.204, 95% confidence interval [CI] 1.057–1.373;
Conclusions
Initiation of enzalutamide as the first ARPI was associated with improved survival, particularly in older and more comorbid patients. These findings suggest that treatment strategy should primarily focus on the selection of the first ARPI rather than on the sequencing of subsequent ARPIs.