Pharmacokinetics and pharmacogenomics of ribociclib in black patients with metastatic breast cancer the LEANORA study

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

doi:10.1038/s41523-024-00692-w

Pharmacokinetics and pharmacogenomics of ribociclib in black patients with metastatic breast cancer the LEANORA study

NPJ Breast Cancer. 2024 Sep 30;10(1):84. doi: 10.1038/s41523-024-00692-w.

Authors

Ilana Schlam^#^{1

2}, D Max Smith^#^{3

4

5}, Cody Peer⁶, Tristan Sissung⁶, Keith T Schmidt^{6

7}, Ming Tan⁸, Ami Chitalia⁹, Nanette H Bishopric³, Seth Steinberg¹⁰, Hyoyoung Choo-Wosoba¹⁰, Giulia Napoli⁷, Christopher Gallagher⁹, Nadia Ashai⁵, Kristen Whitaker⁹, Candace Mainor⁵, Shruti Tiwari¹¹, Nicole Swanson³, Stacy Malloy⁹, Claudine Isaacs^{3

5}, William Douglas Figg^{6

7}, Sandra M Swain^{12

13}

Affiliations

¹ Division of Hematology and Oncology, Tufts Medical Center, Boston, MA, USA.
² Tufts University, Boston, MA, USA.
³ Department of Oncology, Georgetown University Medical Center, Washington, DC, USA.
⁴ MedStar Health, Columbia, MD, USA.
⁵ Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA.
⁶ Clinical Pharmacology Program, National Cancer Institute, Bethesda, MD, USA.
⁷ Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
⁸ Department of Biostatistics, Bioinformatics and Biomathematics, Georgetown University Medical Center, Washington, DC, USA.
⁹ Hematology-Oncology Department, MedStar Washington Hospital Center, Washington, DC, USA.
¹⁰ Office of Collaborative Biostatistics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
¹¹ Virginia Cancer Specialists, Fairfax, VA, USA.
¹² MedStar Health, Columbia, MD, USA. [email protected].
¹³ Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA. [email protected].

^# Contributed equally.

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.

Abstract

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