Therapeutic drug monitoring of osimertinib in EGFR mutant non-small cell lung cancer by dried blood spot and plasma collection: A pilot study.
Br J Clin Pharmacol
; 90(8): 1942-1951, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38706157
ABSTRACT
AIMS:
Therapeutic drug monitoring (TDM) has led to significant improvements in individualized medical care, although its implementation in oncology has been limited to date. Tyrosine kinase inhibitors (TKIs) are a group of therapies for which TDM has been suggested. Osimertinib is one such therapy used in the treatment of epidermal growth factor receptor (EGFR) mutation-driven lung cancer. Herein, we describe a prospective pilot study involving 21 patients on osimertinib primarily as a preliminary evaluation of drug levels in a real-world setting.METHODS:
Concentrations of the drug and its primary metabolites were measured with a validated liquid chromatography-mass spectrometry (LC-MS) assay across serial timepoints. As part of this study, inter-individual variability by dose and ethnicity as well as intra-individual variability across timepoints are explored. Furthermore, we attempted to validate dried blood spot (DBS)-based quantitation as an accurate alternative to plasma quantitation.RESULTS:
Successful quantitation of osimertinib and primary metabolites was achieved for our subjects. Compound plasma levels were highly correlated to DBS levels. There was no significant difference in concentrations with ethnicity or dosing or intra-individual variability across timepoints.CONCLUSIONS:
As such, we demonstrate that TDM for osimertinib is practical for future trials. We also validated the use of DBS as an alternative to conventional quantitation for exploration of TDM for osimertinib in larger trials and for other targeted therapies.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Acrilamidas
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Monitoramento de Medicamentos
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Carcinoma Pulmonar de Células não Pequenas
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Inibidores de Proteínas Quinases
/
Teste em Amostras de Sangue Seco
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Receptores ErbB
/
Compostos de Anilina
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Neoplasias Pulmonares
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Mutação
Limite:
Aged80
Idioma:
En
Revista:
Br J Clin Pharmacol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Austrália
País de publicação:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
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UNITED KINGDOM