Neratinib in ERBB2-positive brain metastases
Mené sur 479 patientes atteintes d'un cancer du sein HER2+ métastatique et/ou récidivant, cet essai international randomisé évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité d'un traitement de première ligne combinant nératinib et paclitaxel par rapport à une combinaison trastuzumab-paclitaxel
Neratinib was originally derived by modication of EKB-569 (pelitinib), an irreversible epidermal growth factor receptor (EGFR) inhibitor. Like other irreversible ERBB family tyrosine kinase inhibitors (TKIs), the chemistry of neratinib is based on a quinolone core with a Michael acceptor moiety designed to form a covalent bond with the conserved cysteine residues at the adenosine triphosphate (ATP) binding sites (Cys-773 and Cys-805) in EGFR and ERBB2 (formerly HER2 or HER2/neu), respectively, resulting in IC50 values of 92nM for EGFR and 59nM for the ERBB2 kinase.
JAMA Oncology 2016