Titre :

A multicenter, phase I, pharmacokinetic study of osimertinib in cancer patients with normal renal function or severe renal impairment.

Auteur(s) :

Vishwanathan, Karthick [Auteur]
AstraZeneca
Sanchez-Simon, Inmaculada [Auteur]
Hospital Universitario Virgen del Rocío [Sevilla]
Keam, Bhumsuk [Auteur]
Seoul National University [Seoul] [SNU]
Penel, Nicolas [Auteur]
METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694
De Miguel-Luken, Maria [Auteur]
Weilert, Doris [Auteur]
IQVIA
Mills, Andrew [Auteur]
AstraZeneca [Cambridge, UK]
Marotti, Marcelo [Auteur]
AstraZeneca [Cambridge, UK]
Ravaud, Alain [Auteur]
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]

Titre de la revue :

Pharmacol Res Perspect

Nom court de la revue :

Pharmacol Res Perspect

Numéro :

8

Pagination :

e00613

Date de publication :

2020-06-27

ISSN :

2052-1707

Mot(s)-clé(s) en anglais :

epidermal growth factor receptors
kidney
non-small cell lung cancer
osimertinib
pharmacokinetics
renal disposition
tyrosine kinase inhibitors

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Osimertinib is a third-generation, irreversible, oral epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR-TKI sensitizing and EGFR T790M and has demonstrated ...
Lire la suite >Osimertinib is a third-generation, irreversible, oral epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR-TKI sensitizing and EGFR T790M and has demonstrated efficacy in non-small cell lung cancer (NSCLC) central nervous system metastases. In this phase I study, we assessed the effects of normal renal function (NRF) and severe renal impairment (SRI) on the pharmacokinetics (PK) of osimertinib in patients with solid tumors. Part A: patients with NRF (creatinine clearance [CrCL] ≥90 mL/min), and SRI, (CrCL <30 mL/min), received a single 80-mg oral dose of osimertinib and standard PK measures were assessed. Part B: patients with SRI were treated for 3 months to obtain safety data, if deemed clinically appropriate. The geometric mean osimertinib plasma concentrations were higher in patients with SRI (n = 7) vs NRF (n = 8) and were highly variable. Osimertinib exposure based on Cmax and area under the plasma concentration-time curve, was 1.19-fold (90% CI: 0.6, 2.0) and 1.85-fold (90% CI: 0.9, 3.6), respectively, higher for patients with SRI vs patients with NRF, with no clear correlation between CrCL and exposure. No new safety signals were identified after 12 weeks of osimertinib 80 mg continuous dosing. PK parameters pooled across this study and other phase I, II, and III osimertinib clinical studies (exploratory population PK analysis), showed minimal correlation between CrCL and total clearance. In conclusion, no dose adjustment is required for osimertinib for patients with SRI.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CHU Lille

Collections :

• METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694

Date de dépôt :

2023-11-15T08:40:59Z
2023-12-14T13:37:11Z