A population pharmacokinetic (PK) model for erlotinib (E), a small molecule inhibitor of the epidermal growth factor receptor (EGFR)

2032 Background: E as a single agent produced a survival benefit in patients with advanced NSCLC after failure of at least one prior chemotherapy regimen. The objective of this analysis was to: 1) describe the PK of E and its active metabolite (OSI-420) using a population approach and 2) identify covariates that impact E PK. Methods: A population PK model was developed using 2670 E concentrations from 708 patients enrolled in 4 Phase II single-agent trials and 2 Phase III trials in combination with chemotherapy. A subsequent analysis was performed using 2576 concentrations in 591 patients from 4 phase II single agent study plus a single-agent Phase III NSCLC trial once its data became available. Results: A one-compartment model described the concentration data well. The covariate effects were similar between the two analyses, where total bilirubin, α-1-glycoprotein, and smoking status were the most important factors affecting clearance (CL/F). The overall contribution of these covariates was modest and ma...