Preclinical Comparison of the Blood-brain barrier Permeability of Osimertinib with Other EGFR TKIs.
Nicola ColcloughKan ChenPeter JohnströmNicole StrittmatterYumei YanGail L WrigleyMagnus SchouRichard J A GoodwinKatarina VarnäsSally J AduaMinghui ZhaoDon X NguyenGareth MaglennonPeter BartonJames AtkinsonLin ZhangAnnika JanefeldtJoanne WilsonAaron SmithAkihiro TakanoRyosuke ArakawaMikhail KondrashovJonas MalmquistEvgeny RevunovAna Vazquez-RomeroMohammad Mahdi MoeinAlbert D WindhorstNatasha A KarpM Raymond V FinlayRichard A WardJames W T YatesPaul D SmithLars FardeZack ChengDarren A E CrossPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2020)
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 in vitro transporter efflux ratios and increased brain penetrance in vivo supporting the use of in vitro transporter assays as an early screen in drug discovery.