Preclinical Comparison of the Blood–brain barrier Permeability of Osimertinib with Other EGFR TKIs

Abstract

These preclinical studies indicate that osimertinib can achieve significant exposure in the brain compared with the other EGFR-TKIs tested and supports the ongoing clinical evaluation of osimertinib for the treatment of EGFR-mutant brain metastasis. This work also demonstrates the link between low <i>in vitro</i> transporter efflux ratios and increased brain penetrance <i>in vivo</i> supporting the use of <i>in vitro</i> transporter assays as an early screen in drug discovery.