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

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 FiggSandra M. Swain^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	84
Journal	npj Breast Cancer
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41523-024-00692-w
State	Published - Dec 2024
Externally published	Yes

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Schlam, I., Smith, D. M., Peer, C., Sissung, T., Schmidt, K. T., Tan, M., Chitalia, A., Bishopric, N. H., Steinberg, S., Choo-Wosoba, H., Napoli, G., Gallagher, C., Ashai, N., Whitaker, K., Mainor, C., Tiwari, S., Swanson, N., Malloy, S., Isaacs, C., ... Swain, S. M. (2024). Pharmacokinetics and pharmacogenomics of ribociclib in black patients with metastatic breast cancer the LEANORA study. npj Breast Cancer, 10(1), Article 84. https://doi.org/10.1038/s41523-024-00692-w

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title = "Pharmacokinetics and pharmacogenomics of ribociclib in black patients with metastatic breast cancer the LEANORA study",

abstract = "Underrepresented populations{\textquoteright} 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{\texttrademark} 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.",

author = "Ilana Schlam and Smith, {D. Max} and Cody Peer and Tristan Sissung and Schmidt, {Keith T.} and Ming Tan and Ami Chitalia and Bishopric, {Nanette H.} and Seth Steinberg and Hyoyoung Choo-Wosoba and Giulia Napoli and Christopher Gallagher and Nadia Ashai and Kristen Whitaker and Candace Mainor and Shruti Tiwari and Nicole Swanson and Stacy Malloy and Claudine Isaacs and Figg, {William Douglas} and Swain, {Sandra M.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = dec,

doi = "10.1038/s41523-024-00692-w",

language = "English",

volume = "10",

journal = "npj Breast Cancer",

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Schlam, I, Smith, DM, Peer, C, Sissung, T, Schmidt, KT, Tan, M, Chitalia, A, Bishopric, NH, Steinberg, S, Choo-Wosoba, H, Napoli, G, Gallagher, C, Ashai, N, Whitaker, K, Mainor, C, Tiwari, S, Swanson, N, Malloy, S, Isaacs, C, Figg, WD & Swain, SM 2024, 'Pharmacokinetics and pharmacogenomics of ribociclib in black patients with metastatic breast cancer the LEANORA study', npj Breast Cancer, vol. 10, no. 1, 84. https://doi.org/10.1038/s41523-024-00692-w

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AU - Schlam, Ilana

AU - Smith, D. Max

AU - Peer, Cody

AU - Sissung, Tristan

AU - Schmidt, Keith T.

AU - Tan, Ming

AU - Chitalia, Ami

AU - Bishopric, Nanette H.

AU - Steinberg, Seth

AU - Choo-Wosoba, Hyoyoung

AU - Napoli, Giulia

AU - Gallagher, Christopher

AU - Ashai, Nadia

AU - Whitaker, Kristen

AU - Mainor, Candace

AU - Tiwari, Shruti

AU - Swanson, Nicole

AU - Malloy, Stacy

AU - Isaacs, Claudine

AU - Figg, William Douglas

AU - Swain, Sandra M.

PY - 2024/12

Y1 - 2024/12

N2 - 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.

AB - 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.

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