Pharmacokinetics and Pharmacogenomics of Ribociclib in Black Patients with Metastatic Breast Cancer: The LEANORA study

TL;DR

This study examines how Black patients metabolize ribociclib, a breast cancer drug, and finds no significant differences in drug exposure based on genetic variations.

Contribution

The study provides pharmacokinetic and pharmacogenomic data for ribociclib in Black patients, a historically underrepresented group in clinical trials.

Findings

CYP3A5 phenotypes varied among participants, but drug exposure levels were similar across metabolizer groups.

No association was found between CYP3A5 genotype and ribociclib exposure in Black patients.

Adverse event rates were consistent regardless of CYP3A5 metabolizer status.

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.