A population pharmacokinetic analysis for BIBF 1120, an angiokinase inhibitor, in patients with advanced non-small-cell lung cancer (NSCLC)

Abstract

14528 Background: BIBF 1120 is a potent angiokinase inhibitor, targeting vascular endothelial, platelet derived and fibroblast growth factor receptor tyrosine kinases. The objective of the population pharmacokinetic (PK) analysis was to describe the PK of BIBF 1120 in patients with advanced/metastatic non-small-cell lung cancer (NSCLC) and to explore the impact of patient factors on the PK parameters of BIBF 1120 using data from a double-blind, randomized Phase II study. Methods: In this double-blind multicenter trial, 73 patients with an Eastern Cooperative Oncology Group (ECOG) score of 0–2 with locally advanced or metastatic (stage IIIB/IV) relapsed NSCLC after failure of first or second line chemotherapy were randomly assigned to continuous twice daily treatment with 150 mg or 250 mg of BIBF 1120 until disease progressionor limiting toxicity. Trough samples for PK analysis were taken at various visits. Sparse absorption profiles were determined at two visits. PK data from 71 patients (736 plasma samples) was available. Demographics, laboratory values and cancer-specific covariates including baseline ECOG score were tested for their effect on PK parameters. The analysis was performed using NONMEM. Results: A one-compartment model with first-order absorption (ka) and elimination rate described the PK data adequately. The slightly delayed absorption was accounted for by a lag time of 20 minutes. Clearance (CL/F), volume of distribution (V/F) and ka were 697 L/h, 8170 L and 1.31h−1, respectively. Interindividual and interoccasion variability estimates for CL/F and V/F were moderate to high. None of the covariates tested showed a clinically relevant effect on the PK parameters of BIBF 1120 and thus none were included in the model. A trend towards lower CL/F values with increased liver enzymes was observed but its effect was small. Conclusions: BIBF 1120 plasma concentrations in NSCLC patients were described by a one-compartment model. No clinically relevant covariates influencing the PK of BIBF 1120 were detected. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Boehringer Ingelheim GmbH & Co. KG Boehringer Ingelheim, Hoffman-La Roche, Lilly, Pharsight Corporation Bayer HealthCare, Boehringer Ingelheim, Hoffman-La Roche, Lilly Boehringer Ingelheim, Pharsight Corporation