Overall survival between veterans with metastatic castration-resistant prostate cancer treated with enzalutamide or abiraterone with kidney disease.
Authors: Robert Wilson, Jason M Doherty, Suhong Luo, Danielle Candelieri-Surette, Daniel B. Eaton, Martin W. Schoen
Journal: Journal of Clinical Oncology (2025)

76 Background: Enzalutamide and abiraterone are androgen receptor pathway inhibitors (ARPIs) used in metastatic castration-resistant prostate cancer (mCRPC). However, little research has compared their efficacy in this population with co-morbid chronic kidney disease (CKD). Since these medications alter androgen signaling differently and abiraterone is co-administered with prednisone, median overall survival (OS) may differ in patients with decreased renal function. Methods: Veterans within the Veterans Health Administration initially treated with abiraterone or enzalutamide for mCRPC between September 8, 2014, and October 9, 2023 were included. Age at treatment initiation, PSA at diagnosis, race, Charlson comorbidity index, and baseline serum creatinine values were acquired for each patient. Patients with an estimated glomerular filtration rate (eGFR) less than 60 mL/min were included in the CKD group. Survival analysis was performed using the Kaplan-Meier method. Cox proportional hazards modeling was used to adjust for differences in baseline characteristics between study groups. Results: We analyzed 10,356 veterans with mCRPC. 1944 (18.8%) had an eGFR less than 60 mL/min and 8412 (81.2%) had an eGFR greater than or equal to 60 mL/min. Of the CKD group, 1093 (56.2%) were treated first with abiraterone and 851 (43.8%) with enzalutamide. The enzalutamide group contained a larger percentage of patients with both cardiovascular disease and diabetes mellitus (47.7% vs. 40.4%, p = 0.06). The abiraterone group had a higher median PSA at diagnosis (7.2 vs 3.9 ng/mL, p &lt; 0.001) and lower median eGFR at treatment initiation (48.82 vs. 49.32 mL/min, p = 0.03). There was no significant difference in median OS between patients treated with abiraterone (n = 4752) or enzalutamide (n = 3660) in the group of patients without CKD (42.9 vs. 44.0 months, p = 0.29). However, in the group of patients with CKD, enzalutamide revealed a longer median OS (35.2 vs 30.5 months, p &lt; 0.001) and decreased mortality when adjusting for differences in baseline characteristics (Adjusted HR 0.80, 95% CI 0.77-0.94). Additionally, patients with CKD were able to take enzalutamide for a longer duration than abiraterone (11 vs. 7 months, p &lt; 0.001). Conclusions: In Veterans with CKD, enzalutamide exhibited longer median OS and decreased risk of death relative to abiraterone. Further research into treatment selection based on comorbid disease could generate revised clinical guidelines that optimize survival in patients with mCRPC. Survival Time Hazard Ratio with 95% CI Adjusted Hazard Ratio with 95% CI CKD Group (n=1944) Enzalutamide (n=851): 35.2 monthsAbiraterone (n=1093): 30.5 monthsp &lt; 0.001 0.835 (0.754 - 0.926) 0.849 (0.766 - 0.941) Non-CKD Group (n=8412) Enzalutamide (n=3660): 44.0 monthsAbiraterone (n=4752): 42.9 monthsp = 0.29 0.944 (0.899 - 0.998) 0.947 (0.899 - 0.998)