Pharmacokinetics and pharmacogenomics of ribociclib in black patients with metastatic breast cancer the LEANORA study
Year: 2024
Type: article
Study design: Observational Study
Abstract: 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.
Source: npj Breast Cancer
Authors: Ilana Schlam, D. Max Smith, Cody Peer, Tristan Sissung, Keith T. Schmidt, Ming Tan, Ami Chitalia, Nanette H. Bishopric, Seth Steinberg, Hyoyoung Choo-Wosoba, Giulia Napoli, Christopher Gallagher, Nadia Ashai, Kristen Whitaker, Candace Mainor, Shruti Tiwari, Nicole Swanson, Stacy Malloy, Claudine Isaacs, William Douglas Figg, Sandra M. Swain
Institutions: Tufts University, Tufts Medical Center, Georgetown University Medical Center, Georgetown Lombardi Comprehensive Cancer Center, MedStar Health, National Cancer Institute, National Institutes of Health, Center for Cancer Research, Georgetown University, MedStar Washington Hospital Center, Virginia Cancer Specialists
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,490
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 Cancer Institute, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: Georgetown-Howard Universities Center for Clinical and Translational Science (GHU, G13596026, G2337728295, G2660551552, G2673235985, Georgetown-Howard Universities Center for Clinical and Translational Science (GHU, G5292387947, G800880157, G9000191194, Georgetown University Lombardi Comprehensive Cancer Center Support Grant
OpenAlex ID: W4403003225