Effects of <i>CYP3A4</i> and <i>CYP2C9</i> genotype on systemic anastrozole and fulvestrant concentrations in SWOG S0226-Reference-Cited by-同舟云学术

Effects of CYP3A4 and CYP2C9 genotype on systemic anastrozole and fulvestrant concentrations in SWOG S0226

Published:2023-08 Issue:12 Volume:24 Page:665-673
ISSN:1462-2416
Container-title:Pharmacogenomics
language:en
Short-container-title:Pharmacogenomics

Author:

Rutherford Delaney V¹^ORCID,Medley Sarah²^ORCID,Henderson Nicholas C²^ORCID,Gersch Christina L¹^ORCID,Vandenberg Ted A³^ORCID,Albain Kathy S⁴^ORCID,Dakhil Shaker R⁵^ORCID,Tirumali Nagendra R⁶,Gralow Julie R⁷^ORCID,Hortobagyi Gabriel N⁸^ORCID,Pusztai Lajos⁹^ORCID,Mehta Rita S¹⁰,Hayes Daniel F¹^ORCID,Kidwell Kelley M²^ORCID,Henry N Lynn¹^ORCID,Barlow William E¹¹^ORCID,Rae James M¹^ORCID,Hertz Daniel L¹²^ORCID

Affiliation:

1. Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA

2. Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA

3. Western University/Canadian Cancer Trials Group, London, ON, N5X 3K8, Canada

4. Loyola University Chicago Stritch School of Medicine, Maywood, IL 60153, USA

5. Cancer Center of Kansas, Wichita, KS 67214, USA

6. Kaiser Permanente, Beaverton, OR 97005, USA

7. American Society of Clinical Oncology, Alexandria, 22314, Virginia

8. University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA

9. Yale School of Medicine, New Haven, CT 06510, USA

10. University of California Irvine Medical Center, Chao Family Comprehensive Cancer Center, Orange, CA 92868, USA

11. SWOG Statistical Center, Seattle, WA 98109, USA

12. Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI 48109, USA

Abstract

Objective & methods: This study tested associations of genotype-predicted activity of CYP3A4, other pharmacogenes, SLC28A7 (rs11648166) and ALPPL2 (rs28845026) with systemic concentrations of the endocrine therapies anastrozole and fulvestrant in SWOG S0226 trial participants. Results: Participants in the anastrozole-only arm with low CYP3A4 activity (i.e. CYP3A4*22 carriers) had higher systemic anastrozole concentrations than patients with high CYP3A4 activity (β-coefficient = 10.03; 95% CI: 1.42, 18.6; p = 0.025). In an exploratory analysis, participants with low CYP2C9 activity had lower anastrozole concentrations and higher fulvestrant concentrations than participants with high CYP2C9 activity. Conclusion: Inherited genetic variation in CYP3A4 and CYP2C9 may affect concentrations of endocrine therapy and may be useful to personalize dosing and improve treatment outcomes.

Funder

Division of Cancer Prevention, National Cancer Institute

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

Link

https://www.futuremedicine.com/doi/pdf/10.2217/pgs-2023-0097

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