Prospective study of UDP-glucuronosyltransferase (UGT) 2B17 genotype and exemestane (Exe) pharmacokinetics (PK) and pharmacodynamics (PD) in Asian, hormone receptor (HR) positive, metastatic breast cancer (MBC) patients.

1056Background: The active metabolite of Exe, 17-dihydroexemestane (17DhExe), is glucuronidated by UGT2B17 to inactive exemestane-17-O-glucuronide (Exe17-O-glu). UGT2B17*2/*2null genotype is 7 times more common in Asians than Caucasians and leads to reduced Exe glucuronidation in vitro. We studied Exe PK and PD in MBC patients genotyped for UGT2B17. Methods: Eligible patients (HR+ MBC; ≥1 line of endocrine therapy) received Exe 25mg OD till progression. UGBT2B17 genotype was correlated with day 29 (D29) steady-state PK (Exe and metabolites), change in PD biomarkers (estrone and androstenedione) at D29 vs baseline (BL), objective response rate (ORR) [sum of complete and partial responses], and clinical benefit rate (CBR) [response or stable disease ≥ 24 weeks]. Results: In 64 patients enrolled, CBR was 25%; ORR was 3%. Frequencies of UGT2B17*2/*2, UGT2B17*1/*2 and UGT2B17*1/*1 were 72%, 26% and 2%, respectively. PD and PK data were available for 54 and 53 patients respectively. Mean Exe17-O-glu AUC and Cma...