TY - JOUR AU - Tran, Phu N. AU - Klempner, Samuel J. PY - 2017 TI - ALK on my mind: alectinib takes an early lead in managing intracranial disease in non-small cell lung cancer with ALK rearrangements JF - Annals of Translational Medicine; Vol 5, No 7 (April 14, 2017): Annals of Translational Medicine Y2 - 2017 KW - N2 - Non-small cell lung cancers (NSCLC) harboring oncogenic anaplastic lymphoma kinase fusions (ALK+) embody the paradigm and success of precision medicine. Despite high overall response rates (ORR) with the first ALK inhibitor crizotinib, a pattern of central nervous system (CNS) failure emerged, highlighting the need for CNS-specific study and assessment. In fact, the CNS is the first site of progressive disease (PD) in nearly 70% of ALK+ patients taking crizotinib (1). Unlike crizotinib and ceritinib, alectinib is not a substrate of P -glycoprotein, a key efflux transporter that hinders drug penetration through the blood-brain barrier (BBB) and may partly underlie observations of pharmacologic failure (2,3). The ratio of alectinib to plasma in cerebrospinal fluid (CSF) approaches 0.75 indicating a very high degree of CNS penetration (4). Early small data sets showed that the intracranial response rate of alectinib ranged from 40% to 57% ( Table 1 ) (14). Additionally, alectinib was reported to have activity in ALK+ NSCLC patients with leptomeningeal disease (15,16). UR - https://atm.amegroups.org/article/view/14036