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

  • Res Sq. 2024 Aug 13:rs.3.rs-4656461. doi: 10.21203/rs.3.rs-4656461/v1.
Sandra Swain  1 ,  Ilana Schlam  2 ,  D Max Smith  3 ,  Cody Peer  4 ,  Tristan Sissung  4 ,  Keith Schmidt  5 ,  Ming Tan  6 ,  Ami Chitalia  7 ,  Nanette Bishopric  8 ,  Seth Steinberg  9 ,  Hyoyoung Choo-Wosoba  10 ,  Giulia Napoli  11 ,  Christopher Gallagher  12 ,  Nadia Ashai  13 ,  Kristen Whitaker  7 ,  Candace Mainor  13 ,  Shruti Tiwari  14 ,  Nicole Swanson  8 ,  Stacy Malloy  7 ,  Claudine Isaacs  15 ,  William Figg  4
Affiliations
  • 1. Georgetown University Medical Center.
  • 2. Division of Hematology and Oncology.
  • 3. Department of Oncology.
  • 4. Clinical Pharmacology Program, National Cancer Institute.
  • 5. Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute.
  • 6. Department of Biostatistics, Bioinformatics and Biomathematics.
  • 7. Hematology-Oncology Department, MedStar Washington Hospital Center.
  • 8. Department of Oncology, Georgetown University Medical Center.
  • 9. Office of Collaborative Biostatistics, Center for Cancer Research, National Cancer Institute.
  • 10. Office of Collaborative Biostatistics, Center for Cancer Research, National Cancer Institute, National Institutes of Health.
  • 11. Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health.
  • 12. MedStar Washington Hospital Center.
  • 13. Georgetown Lombardi Comprehensive Cancer Center.
  • 14. Virginia Cancer Specialists.
  • 15. Georgetown University.
PMID: 39184092 DOI: 10.21203/rs.3.rs-4656461/v1
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.

Keywords
Black/African American; CYP3A5; breast cancer; pharmacokinetics and pharmacogenomics; race; ribociclib.
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