In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 1056-1056
Abstract:
1056 Background: 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 C max were significantly lower, and mean 17DhExe C max numerically higher in patients with UGT2B17*2/*2 vs other genotypes (Table 1). 17DhExe C max was higher in patients with clinical benefit vs none (5.6 vs 3.8 ng/ml, p=0.02). Frequency of desired PD effect (rise in androstenedione and fall in estrone at D29 vs BL) was 22%. Exe plasma active index (PAI) [Table 1] was higher in patients with a fall in D29 estrone vs those without (14.7 vs 9.5, p=0.05). Conclusions: UGT2B17 genotype affects Exe PK and may have significant PD correlates. Larger studies to examine effects on clinical treatment efficacy are needed. Clinical trial information: NCT01655004. [Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.15_suppl.1056
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
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