Frequency of liver test increases on abiraterone acetate in men with castrate-resistant prostate cancer (CRPC): Natural history, management, and outcome.

Abstract

332 Background: Abiraterone acetate (abiraterone) in combination with prednisone is a standard of care for patients with metastatic CRPC. Abiraterone is seldom associated with liver toxicity and systematic monitoring of ALT and AST is required. Clinical management and outcome of these patients have not been described. Methods: We retrospectively identified 22 men with mCRPC with liver tests disorder occurring during abiraterone therapy from December 2009 to September 2017 from three oncology centers in France. Results: Thirty nine liver disorder events occurred in 22 patients during abiraterone therapy. The median age was 62 (50-80) years. Only one patient had liver metastasis. No patient had a history of chronic alcoholism. Accountability of the liver tests increase to abiraterone was doubtful in two patients who were receiving antibiotics when the event occurred. The incidence of AST increase (19 events) and that of ALT (20 events) were similar. Liver toxicity was of grade 1, 2, and 3 (CTCAEv4) in 5 (22.7%), 5 (22.7%), and 9 (40.9%) patients for ALT, and in 9 (40.9%), 6 (27.3%), and 5 (22.7%) for AST, respectively. The median time from abiraterone initiation to the detection of liver toxicity was 15.8 (4-95) weeks. The median time from highest ALT/AST increase to normalization was 7.7 (2-15) weeks. Normalization of liver test was observed in 19 (86.4%) patients, and 3 patients died of cancer progression before their liver tests had normalized. In 12 patients (54.4%), liver tests spontaneously returned to baseline values, while abiraterone was continued at full dose. Abiraterone was discontinued in 6 patients (27.7%) due to liver test increase. It was reintroduced after a break in four patients and then discontinued in two for a subsequent liver disorder event. No patient reported symptoms clearly related to liver test increase. Conclusions: Liver tests increase is a quite rare event that typically occurs within the first 4 months on abiraterone, though it can also happen up to 20 months later. It is typically asymptomatic and most patients experience normalization of tests, either spontaneously or after dose reduction/discontinuation.