Early discontinuation of abiraterone acetate/prednisone (AA/P) in localized prostate cancer.

Abstract

e17003 Background: Data from STAMPEDE trial supporting systemic therapy intensification with long course AA/P was first presented in 2017. Overall survival benefit was confirmed in 2021. Our institution proceeded with early adoption of addition of 24 months of AA/P to ADT and radiotherapy (RT) in patients with high-risk localized or regional prostate cancer in 2017. In STAMPEDE, only 17% patients discontinued AA/P prior to completion of planned course. Outside of a clinical trial, whether patients adhere to this intense combination therapy that is associated with toxicities and expense is unknown. We hypothesized that adherence to long course AA/P in real-world practice in definitively treated prostate cancer would be poor. Methods: We performed a retrospective study for patients with clinically localized prostate cancer treated with AA/P combined with standard ADT and RT who had at least 6 months of follow-up data. Primary endpoint was rate of early discontinuation (prior to the 24mo) of AA/P. Secondary outcomes included rates of RT completion and disease recurrence and toxicity of intensive therapy. Reasons for early discontinuation were analyzed. Fisher's Exact, Chi-square analysis and Mann-Whitney tests were used to compare variables. SAS 9.4 was used for statistical analysis. Results: We identified 77 patients who met inclusion criteria, including 2 (2%) with high-risk, 30 (39%) with very high-risk, 19 (25%) with regional risk and 26 (34%) with locally recurrent disease after prostatectomy. AA/P was discontinued in 29 (38%) patients prior to completion of 24mo. Among those with early discontinuation, median duration of AA/P was 12.1 mo [0.1-21.7] and median duration of ADT was 17 mo[3.5-32.2]. Common reasons for early AA/P discontinuation included refractory hypokalemia (n = 4), diarrhea (n = 3), heart failure and fluid retention (n = 2 each) and quality of life deterioration (n = 8). Other reasons included hepatotoxicity, arrhythmia, osteoporotic fracture and financial toxicity (n = 1 each). All patients completed definitive RT. Only 1 of 77 patients had disease recurrence and had discontinued AA/P after 14 mo. A statistically significant association between age at diagnosis and treatment completion was noted(p = 0.01); each 1-year increase in age was associated with 9.4% decrease in odds of completing AA/P. Median age at diagnosis in those completing vs not completing AA/P was 65 vs 71 years. Conclusions: Very high rates of early discontinuation of AA/P were observed among patients with localized prostate cancer receiving definitive RT. Patients were less tolerant of toxicity in adjuvant setting compared to in a clinical trial or advanced disease. Shorter durations of AA/P appeared more acceptable but whether similar benefit is derived with a truncated course of AA/P is unknown. Future studies need to explore an optimal duration of AA/P that will reduce toxicity without compromising survival benefit.