Exposure–Response Analysis of Osimertinib in EGFR Mutation Positive Non-Small Cell Lung Cancer Patients in a Real-Life Setting

Background Osimertinib, an irreversible inhibitor of the epidermal growth factor receptor (EGFR) is an important drug in the treatment of EGFR-mutation positive non-small cell lung cancer (NSCLC). Clinical trials with osimertinib could not demonstrate an exposure-efficacy relationship, while a relat...

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Bibliographic Details
Published in:Pharmaceutical research 2022-10, Vol.39 (10), p.2507-2514
Main Authors: Boosman, René J., Jebbink, Merel, Veldhuis, Wouter B., Groenland, Stefanie L., van Veggel, Bianca A. M. H., Moeskops, Pim, de Langen, Adrianus J., Beijnen, Jos H., Smit, Egbert F., Huitema, Alwin D. R., Steeghs, Neeltje
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
Care and treatment
Clinical trials
Dosage
Drug dosages
Epidermal growth factor
Epidermal growth factor receptors
Genetic aspects
Lung cancer
Lung cancer, Non-small cell
Lung cancer, Small cell
Medical Law
Medical research
Medicine, Experimental
Multivariate analysis
Mutation
Non-small cell lung carcinoma
Original Research Article
Patients
Pharmacokinetics
Pharmacology/Toxicology
Pharmacy
Small cell lung carcinoma
Statistical analysis
Targeted cancer therapy
Toxicity
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Summary:Background Osimertinib, an irreversible inhibitor of the epidermal growth factor receptor (EGFR) is an important drug in the treatment of EGFR-mutation positive non-small cell lung cancer (NSCLC). Clinical trials with osimertinib could not demonstrate an exposure-efficacy relationship, while a relationship between exposure and toxicity has been found. In this study, we report the exposure–response relationships of osimertinib in a real-life setting. Methods A retrospective observational cohort study was performed, including patients receiving 40 - 80 mg osimertinib as ≥ 2 line therapy and from whom pharmacokinetic samples were collected during routine care. Trough plasma concentrations (C min,pred ) were estimated and used as a measure of osimertinib exposure. A previously defined exploratory pharmacokinetic threshold of 166 µg/L was taken to explore the exposure-efficacy relationship. Results A total of 145 patients and 513 osimertinib plasma concentration samples were included. Median progression free survival (PFS) was 13.3 (95% confidence interval (CI):10.3 – 19.1) months and 9.3 (95% CI: 7.2 – 11.1) months for patients with C min,pred  
ISSN:0724-8741
1573-904X
DOI:10.1007/s11095-022-03355-2