Abiraterone acetate in metastatic castration-resistant prostate cancer: a retrospective review of the Princess Margaret experience of (I) low dose abiraterone and (II) prior ketoconazole

Introduction: Abiraterone (AA) is a CYP17 inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC). Data suggest similar pharmacokinetics of 250-500 mg of AA with high-fat meals ('low-dose') and 1000 mg in the fasting state ('full-dose'). Ketoconazole (KT) is a less potent CYP17 inhibitor previously widely used in mCRPC.

Objective: To study outcomes of men with mCRPC treated with low-dose AA and/or with prior exposure to KT.

Patients and methods: Retrospective chart review of all men treated with AA at the Princess Margaret Cancer Centre between November 2009 and March 2013. Outcome measures were prostate-specific antigen response rate (PSA-RR), biochemical progression-free survival (bPFS), treatment duration and overall survival (OS). Associations between AA dose or prior KT and outcomes were assessed using chi-square test for PSA-RR and log-rank test for bPFS, treatment duration and OS.

Results: In total, 111 men who received AA were evaluable, of which 21 received low-dose AA and 23 received prior KT. There was a non-significant difference in PSA-RR (43% versus 32%, p=0.37), but no significant differences in median bPFS, median treatment duration and median OS (18.7 versus 16.6 months, p=0.25) in the full and low-dose cohorts respectively, and for those who received prior KT or not (PSA-RR 48% versus 38%, p=0.4; median OS 24.2 versus 16.5 months, p=0.066, respectively).

Conclusions: Low-dose AA or prior KT treatment were not associated with poorer outcome in men with mCRPC treated with AA. These observations may have implications for drug sequencing and dose in resource-limited settings.