Effect of prednisone dosing on mineralocorticoid-related side effects with abiraterone in prostate cancer.

Abstract

67 Background: Abiraterone, a 17a hydroxylase inhibitor, is used for prostate cancer and can lead to mineralocorticoid excess syndrome (e.g. hypertension and hypokalemia). Concurrent prednisone mitigates these effects; however, the optimal prednisone dosage is unclear. This study examines the occurrence of mineralocorticoid side effects from Abiraterone with 5 mg of prednisone daily versus 5 mg twice daily. Methods: Data for 1410 patients treated with abiraterone from 2011 to 2022 were identified from a large academic/community hospital system (Health Data Compass Data Warehouse project). Laboratory measures, clinical parameters, and ICD10 codes were collected from 6 months prior to abiraterone initiation through treatment duration. 348 patients were excluded for missing medication data, discordant prednisone initiation, and use of a second steroid; 1062 patients remained (5 mg daily, N = 555, 10 mg daily, N = 507). Prednisone dose was treated as a time-varying covariate due to dose-switching (N = 122). Hypokalemia and hypertension incidence over 24 weeks after abiraterone initiation was analyzed via time to event frailty cox-proportional hazard models using both CTCAE v5.0 grade and ICD 10 code outcomes. Results: Patients on 5 mg of prednisone twice daily had approximately a 96% longer average time to first event for a combined-endpoint of hypertension and hypokalemia via ICD10 code methodology at any point during the 24 weeks following abiraterone initiation (HR 0.51, CI 0.43 - 0.62, P < 0.001). This trend was durable with individual ICD10 analysis in hypertension (HR 0.52, CI 0.43 - 0.62, P < 0.001) and hypokalemia (HR 0.45, CI 0.30 - 0.66, P = <0.001). Assessing direct clinical measurements via incidentally recorded blood pressure and potassium lab values, the analysis for grade 2/3 hypertension (HR 0.81, CI 0.7-0.93, P = 0.004) and grade 3 hypokalemia (HR 0.46, CI 0.26-0.82, P = 0.008) also showed a corresponding increase in average time to first measure favoring the 5 mg twice daily cohort during the 24-week period. Conclusions: This study shows a significant delay in the development of hypertension and hypokalemia from abiraterone with 5 mg twice daily compared to 5 mg of prednisone daily. This was observed both with ICD10 coding and direct clinical measurements of these events within the EMR. Assessments of other physiologic parameters and survival are ongoing. These findings highlight the impact of prednisone dosing with abiraterone, which may merit additional consideration in specific at-risk patient populations including those with baseline hypertension or cardiovascular risk factors.