Pharmacokinetics and pharmacogenomics of ribociclib in black patients with metastatic breast cancer the LEANORA study
Underrepresented populations' participation in clinical trials remains limited, and the potential impact of genomic variants on drug metabolism remains elusive. This study aimed to assess the pharmacokinetics (PK) and pharmacogenomics (PGx) of ribociclib in self-identified Black women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2) advanced breast cancer. LEANORA (NCT04657679) was a prospective, observational, multicenter cohort study involving 14 Black women. PK and PGx were evaluated using tandem mass spectrometry and PharmacoScan™ microarray (including CYP3A5*3, *6, and *7). CYP3A5 phenotypes varied among participants: 7 poor metabolizers (PM), 6 intermediate metabolizers (IM), and one normal metabolizer (NM). The area under the curve did not significantly differ between PMs (39,230 h*ng/mL) and IM/NMs (43,546 h*ng/mL; p = 0.38). The incidence of adverse events (AEs) was also similar. We found no association between CYP3A5 genotype and ribociclib exposure. Continued efforts are needed to include diverse populations in clinical trials to ensure equitable treatment outcomes.
Authors
- Cody Peer
- Shruti Tiwari (ORCID: https://orcid.org/0000-0003-4873-5666)
- Candace Mainor (ORCID: https://orcid.org/0000-0002-4431-7101)
- Ami Chitalia (ORCID: https://orcid.org/0009-0001-0274-2150)
- Keith Thomas Schmidt (ORCID: https://orcid.org/0009-0008-0285-0216)
- Ming Tan (ORCID: https://orcid.org/0000-0003-2533-8246)
- Ilana Schlam (ORCID: https://orcid.org/0000-0003-4996-0400)
- Nanette H. Bishopric (ORCID: https://orcid.org/0000-0002-8398-5997)
- Seth M. Steinberg (ORCID: https://orcid.org/0000-0002-8280-551X)
- Stacy Malloy
- Tristan M. Sissung (ORCID: https://orcid.org/0000-0002-3684-5377)
- Nadia Ashai (ORCID: https://orcid.org/0000-0002-2952-6941)
- Nicole Swanson
- Sandra M. Swain (ORCID: https://orcid.org/0000-0002-1320-3830)
- Claudine J. Isaacs (ORCID: https://orcid.org/0000-0002-9646-1260)
- Hyoyoung Choo‐Wosoba (ORCID: https://orcid.org/0000-0002-8756-1016)
- Kristen Whitaker (ORCID: https://orcid.org/0000-0002-8084-3838)
- William D. Figg (ORCID: https://orcid.org/0000-0003-2428-5613)
- Dylan M. Smith (ORCID: https://orcid.org/0000-0003-3303-4840)
- Giulia Napoli (ORCID: https://orcid.org/0009-0006-0279-730X)
- Christopher Gallagher (ORCID: https://orcid.org/0000-0002-3846-5052)
Institutions
- Tufts University (US)
- MedStar Washington Hospital Center (US)
- Tufts Medical Center (US)
- National Institutes of Health (US)
- Georgetown University (US)
- Georgetown University Medical Center (US)
- Washington Hospital (US)
- MedStar Georgetown University Hospital (US)
- Office of the Director (US)
- Virginia Cancer Specialists (US)
- National Cancer Institute (US)
- Center for Cancer Research (US)
- Georgetown Lombardi Comprehensive Cancer Center
- MedStar Health (US)
Publication Details
- Journal
- npj Breast Cancer
- Published
- 2024-09-30
- DOI
- https://doi.org/10.1038/s41523-024-00692-w
- Primary Topic
- Advanced Breast Cancer Therapies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Health and Human Services
- Conquer Cancer Foundation
- Breast Cancer Research Foundation
- American Society of Clinical Oncology
- Georgia Clinical and Translational Science Alliance
- National Institutes of Health
- Lombardi Comprehensive Cancer Center, Georgetown University
- National Center for Advancing Translational Sciences