Pharmacokinetic Study of Osimertinib in Cancer Patients with Mild or Moderate Hepatic Impairment.


Journal

The Journal of pharmacology and experimental therapeutics
ISSN: 1521-0103
Titre abrégé: J Pharmacol Exp Ther
Pays: United States
ID NLM: 0376362

Informations de publication

Date de publication:
05 2019
Historique:
received: 21 12 2018
accepted: 20 02 2019
pubmed: 16 3 2019
medline: 21 12 2019
entrez: 16 3 2019
Statut: ppublish

Résumé

Osimertinib, an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), undergoes significant hepatic elimination. In this phase 1 study, we assessed the effects of mild and moderate hepatic impairment on the pharmacokinetics (PK) of osimertinib in patients with malignant solid tumors. In part A, patients with normal hepatic function, mild hepatic impairment, and moderate hepatic impairment, according to the Child-Pugh classification, received a single 80 mg oral dose of osimertinib. Standard PK measures were assessed. In part B, patients could continue osimertinib treatment if deemed clinically appropriate. We compared these study results with a population PK analysis including other osimertinib clinical studies. Geometric mean osimertinib plasma concentrations were lower in patients with mild (

Identifiants

pubmed: 30872388
pii: jpet.118.255919
doi: 10.1124/jpet.118.255919
doi:

Substances chimiques

Acrylamides 0
Aniline Compounds 0
osimertinib 3C06JJ0Z2O

Banques de données

ClinicalTrials.gov
['NCT02161770']

Types de publication

Clinical Trial, Phase I Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

291-299

Subventions

Organisme : NCI NIH HHS
ID : P30 CA054174
Pays : United States

Informations de copyright

Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics.

Auteurs

Enrique Grande (E)

Medical Oncology Department, Ramón y Cajal Hospital, Madrid, Spain (E.G.); Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia (R.D.H., S.S.R.); Medical Oncology, Faculté de Médecine Lyon-Sud, Université Claude Bernard Lyon-1, Institute de Cancérologie des Hospices Civils de Lyon, Lyon, France (B.Y.); Medical Oncology Department, La Paz University Hospital, Autonoma University of Madrid (affiliated with CIBERONC-Instituto de Salud Carlos III), Madrid, Spain (J.F.B.); IQVIA, Kansas City, Missouri (H.G.); Institute for Drug Development, Mays Cancer Center at University of Texas, Health San Antonio, San Antonio, Texas (J.S.); Global Medicines Development, AstraZeneca, Cambridge, United Kingdom (H.M., K.S.); and Quantitative Clinical Pharmacology, Early Clinical Development IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom (M.J., K.V.).

R Donald Harvey (RD)

Medical Oncology Department, Ramón y Cajal Hospital, Madrid, Spain (E.G.); Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia (R.D.H., S.S.R.); Medical Oncology, Faculté de Médecine Lyon-Sud, Université Claude Bernard Lyon-1, Institute de Cancérologie des Hospices Civils de Lyon, Lyon, France (B.Y.); Medical Oncology Department, La Paz University Hospital, Autonoma University of Madrid (affiliated with CIBERONC-Instituto de Salud Carlos III), Madrid, Spain (J.F.B.); IQVIA, Kansas City, Missouri (H.G.); Institute for Drug Development, Mays Cancer Center at University of Texas, Health San Antonio, San Antonio, Texas (J.S.); Global Medicines Development, AstraZeneca, Cambridge, United Kingdom (H.M., K.S.); and Quantitative Clinical Pharmacology, Early Clinical Development IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom (M.J., K.V.).

Benoit You (B)

Medical Oncology Department, Ramón y Cajal Hospital, Madrid, Spain (E.G.); Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia (R.D.H., S.S.R.); Medical Oncology, Faculté de Médecine Lyon-Sud, Université Claude Bernard Lyon-1, Institute de Cancérologie des Hospices Civils de Lyon, Lyon, France (B.Y.); Medical Oncology Department, La Paz University Hospital, Autonoma University of Madrid (affiliated with CIBERONC-Instituto de Salud Carlos III), Madrid, Spain (J.F.B.); IQVIA, Kansas City, Missouri (H.G.); Institute for Drug Development, Mays Cancer Center at University of Texas, Health San Antonio, San Antonio, Texas (J.S.); Global Medicines Development, AstraZeneca, Cambridge, United Kingdom (H.M., K.S.); and Quantitative Clinical Pharmacology, Early Clinical Development IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom (M.J., K.V.).

Jaime Feliu Batlle (JF)

Medical Oncology Department, Ramón y Cajal Hospital, Madrid, Spain (E.G.); Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia (R.D.H., S.S.R.); Medical Oncology, Faculté de Médecine Lyon-Sud, Université Claude Bernard Lyon-1, Institute de Cancérologie des Hospices Civils de Lyon, Lyon, France (B.Y.); Medical Oncology Department, La Paz University Hospital, Autonoma University of Madrid (affiliated with CIBERONC-Instituto de Salud Carlos III), Madrid, Spain (J.F.B.); IQVIA, Kansas City, Missouri (H.G.); Institute for Drug Development, Mays Cancer Center at University of Texas, Health San Antonio, San Antonio, Texas (J.S.); Global Medicines Development, AstraZeneca, Cambridge, United Kingdom (H.M., K.S.); and Quantitative Clinical Pharmacology, Early Clinical Development IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom (M.J., K.V.).

Hal Galbraith (H)

Medical Oncology Department, Ramón y Cajal Hospital, Madrid, Spain (E.G.); Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia (R.D.H., S.S.R.); Medical Oncology, Faculté de Médecine Lyon-Sud, Université Claude Bernard Lyon-1, Institute de Cancérologie des Hospices Civils de Lyon, Lyon, France (B.Y.); Medical Oncology Department, La Paz University Hospital, Autonoma University of Madrid (affiliated with CIBERONC-Instituto de Salud Carlos III), Madrid, Spain (J.F.B.); IQVIA, Kansas City, Missouri (H.G.); Institute for Drug Development, Mays Cancer Center at University of Texas, Health San Antonio, San Antonio, Texas (J.S.); Global Medicines Development, AstraZeneca, Cambridge, United Kingdom (H.M., K.S.); and Quantitative Clinical Pharmacology, Early Clinical Development IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom (M.J., K.V.).

John Sarantopoulos (J)

Medical Oncology Department, Ramón y Cajal Hospital, Madrid, Spain (E.G.); Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia (R.D.H., S.S.R.); Medical Oncology, Faculté de Médecine Lyon-Sud, Université Claude Bernard Lyon-1, Institute de Cancérologie des Hospices Civils de Lyon, Lyon, France (B.Y.); Medical Oncology Department, La Paz University Hospital, Autonoma University of Madrid (affiliated with CIBERONC-Instituto de Salud Carlos III), Madrid, Spain (J.F.B.); IQVIA, Kansas City, Missouri (H.G.); Institute for Drug Development, Mays Cancer Center at University of Texas, Health San Antonio, San Antonio, Texas (J.S.); Global Medicines Development, AstraZeneca, Cambridge, United Kingdom (H.M., K.S.); and Quantitative Clinical Pharmacology, Early Clinical Development IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom (M.J., K.V.).

Suresh S Ramalingam (SS)

Medical Oncology Department, Ramón y Cajal Hospital, Madrid, Spain (E.G.); Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia (R.D.H., S.S.R.); Medical Oncology, Faculté de Médecine Lyon-Sud, Université Claude Bernard Lyon-1, Institute de Cancérologie des Hospices Civils de Lyon, Lyon, France (B.Y.); Medical Oncology Department, La Paz University Hospital, Autonoma University of Madrid (affiliated with CIBERONC-Instituto de Salud Carlos III), Madrid, Spain (J.F.B.); IQVIA, Kansas City, Missouri (H.G.); Institute for Drug Development, Mays Cancer Center at University of Texas, Health San Antonio, San Antonio, Texas (J.S.); Global Medicines Development, AstraZeneca, Cambridge, United Kingdom (H.M., K.S.); and Quantitative Clinical Pharmacology, Early Clinical Development IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom (M.J., K.V.).

Helen Mann (H)

Medical Oncology Department, Ramón y Cajal Hospital, Madrid, Spain (E.G.); Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia (R.D.H., S.S.R.); Medical Oncology, Faculté de Médecine Lyon-Sud, Université Claude Bernard Lyon-1, Institute de Cancérologie des Hospices Civils de Lyon, Lyon, France (B.Y.); Medical Oncology Department, La Paz University Hospital, Autonoma University of Madrid (affiliated with CIBERONC-Instituto de Salud Carlos III), Madrid, Spain (J.F.B.); IQVIA, Kansas City, Missouri (H.G.); Institute for Drug Development, Mays Cancer Center at University of Texas, Health San Antonio, San Antonio, Texas (J.S.); Global Medicines Development, AstraZeneca, Cambridge, United Kingdom (H.M., K.S.); and Quantitative Clinical Pharmacology, Early Clinical Development IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom (M.J., K.V.).

Karen So (K)

Medical Oncology Department, Ramón y Cajal Hospital, Madrid, Spain (E.G.); Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia (R.D.H., S.S.R.); Medical Oncology, Faculté de Médecine Lyon-Sud, Université Claude Bernard Lyon-1, Institute de Cancérologie des Hospices Civils de Lyon, Lyon, France (B.Y.); Medical Oncology Department, La Paz University Hospital, Autonoma University of Madrid (affiliated with CIBERONC-Instituto de Salud Carlos III), Madrid, Spain (J.F.B.); IQVIA, Kansas City, Missouri (H.G.); Institute for Drug Development, Mays Cancer Center at University of Texas, Health San Antonio, San Antonio, Texas (J.S.); Global Medicines Development, AstraZeneca, Cambridge, United Kingdom (H.M., K.S.); and Quantitative Clinical Pharmacology, Early Clinical Development IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom (M.J., K.V.).

Martin Johnson (M)

Medical Oncology Department, Ramón y Cajal Hospital, Madrid, Spain (E.G.); Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia (R.D.H., S.S.R.); Medical Oncology, Faculté de Médecine Lyon-Sud, Université Claude Bernard Lyon-1, Institute de Cancérologie des Hospices Civils de Lyon, Lyon, France (B.Y.); Medical Oncology Department, La Paz University Hospital, Autonoma University of Madrid (affiliated with CIBERONC-Instituto de Salud Carlos III), Madrid, Spain (J.F.B.); IQVIA, Kansas City, Missouri (H.G.); Institute for Drug Development, Mays Cancer Center at University of Texas, Health San Antonio, San Antonio, Texas (J.S.); Global Medicines Development, AstraZeneca, Cambridge, United Kingdom (H.M., K.S.); and Quantitative Clinical Pharmacology, Early Clinical Development IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom (M.J., K.V.).

Karthick Vishwanathan (K)

Medical Oncology Department, Ramón y Cajal Hospital, Madrid, Spain (E.G.); Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia (R.D.H., S.S.R.); Medical Oncology, Faculté de Médecine Lyon-Sud, Université Claude Bernard Lyon-1, Institute de Cancérologie des Hospices Civils de Lyon, Lyon, France (B.Y.); Medical Oncology Department, La Paz University Hospital, Autonoma University of Madrid (affiliated with CIBERONC-Instituto de Salud Carlos III), Madrid, Spain (J.F.B.); IQVIA, Kansas City, Missouri (H.G.); Institute for Drug Development, Mays Cancer Center at University of Texas, Health San Antonio, San Antonio, Texas (J.S.); Global Medicines Development, AstraZeneca, Cambridge, United Kingdom (H.M., K.S.); and Quantitative Clinical Pharmacology, Early Clinical Development IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom (M.J., K.V.) karthick.vishwanathan@astrazeneca.com.

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