| Autor: |
Malhi, Vikram, Nowicka, Malgorzata, Chen, Ya-Chi, Agarwal, Priya, Waldvogel, Marie, Lien, Yi Ting Kayla, Hafner, Marc, Perez-Moreno, Pablo, Moore, Heather M., Yu, Jiajie |
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| Zdroj: |
Cancer Chemotherapy & Pharmacology; Jul2024, Vol. 94 Issue 1, p117-122, 6p |
| Abstrakt: |
Purpose: Giredestrant is a potent, orally bioavailable, small-molecule selective estrogen receptor antagonist and degrader (SERD) that is being developed for the treatment of patients with estrogen receptor (ER)-positive breast cancer. In vitro, giredestrant was primarily metabolized by UGT1A4. The goal of this study was to investigate if UGT1A4 polymorphism had a clinically relevant impact on giredestrant exposure. Methods: Genotyping and pharmacokinetic data were obtained from 118 and 61 patients in two clinical studies, GO39932 [NCT03332797] and acelERA Breast Cancer [NCT04576455], respectively. Results: The overall allelic frequencies of UGT1A4*2 and UGT1A4*3 were 3.3% and 11%, respectively. Giredestrant exposure was consistent between patients with wild-type UGT1A4 and UGT1A4*2 and *3 polymorphisms, with no clinically relevant difference observed. In addition, haplotype analysis indicated that no other UGT1A4 variants were significantly associated with giredestrant exposure. Conclusion: Therefore, this study indicates that UGT1A4 polymorphism status is unlikely a clinically relevant factor to impact giredestrant exposure and giredestrant can be administered at the same dose level regardless of patients' UGT1A4 polymorphism status. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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