Osimertinib Optimal Dosing Through Population Pharmacokinetics in Virtual Patients with NSCLC: An Approach Integrating Multiple Studies

Background/Objectives: Osimertinib is a third-generation tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) T790M mutations in metastatic non-small cell lung cancer (NSCLC). A comprehensive population pharmacokinetic (popPK) model may inform dosing across patient populations. The objective was to develop an integrated popPK model for osimertinib in virtual patients with NSCLC and to evaluate the influence of patient characteristics on PK variability.

Methods

Data were extracted from four published popPK studies of osimertinib in patients with NSCLC. A virtual cohort of 1000 patients from each study was simulated using the corresponding final popPK model, with covariate distributions reconstructed from the reported demographics, resulting in a total virtual cohort of 4000 patients. The primary outcome was the development of a popPK model using nonlinear mixed-effects modeling. Demographic and clinical covariates were evaluated for effects on PK variability.