
==== Front
Res Sq
ResearchSquare
Research Square
2693-5015
American Journal Experts

39184092
10.21203/rs.3.rs-4656461/v1
10.21203/rs.3.rs-4656461
preprint
1
Article
Pharmacokinetics and Pharmacogenomics of Ribociclib in Black Patients with Metastatic Breast Cancer: The LEANORA study
Swain Sandra https://orcid.org/0000-0002-1320-3830

Schlam* Ilana
Smith* D. Max
Peer Cody
Sissung Tristan
Schmidt Keith
Tan Ming
Chitalia Ami
Bishopric Nanette
Steinberg Seth
Choo-Wosoba Hyoyoung
Napoli Giulia
Gallagher Christopher https://orcid.org/0000-0002-3846-5052

Ashai Nadia
Whitaker Kristen
Mainor Candace
Tiwari Shruti
Swanson Nicole
Malloy Stacy
Isaacs Claudine https://orcid.org/0000-0002-9646-1260

Figg William
13 8 2024
rs.3.rs-4656461https://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
https://www.researchsquare.com/article/rs-4656461/v1
nihpp-rs4656461v1.pdf
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 hr*ng/mL) and IM/NMs (43,546 hr*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.
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