Encorafenib and Binimetinib: A New Treatment Option for BRAFV600E-Mutant Non–Small-Cell Lung Cancer

Mené sur 98 patients atteints d'un cancer du poumon non à petites cellules de stade métastatique et présentant la mutation V600 au niveau du gène BRAF, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'un traitement combinant encorafénib et binimétinib

Résumé en anglais

The identification of oncogenic drivers and the development of targeted therapies improved the outcomes of patients with metastatic non–small-cell lung cancer (NSCLC). These therapeutic advances established the role of molecular testing in routine clinical care, and the division of NSCLC into molecular subtypes.1 The incidence of BRAF mutations in NSCLC is estimated to be 1%-3% in NSCLC with adenocarcinoma histology, and approximately half of the mutations are BRAFV600E mutations.2-4 BRAF mutations are observed in patients with a history of current or prior tobacco use, which differs from some of the other oncogenic driver alterations. BRAF is a serine/threonine kinase that transduces signals downstream of the RAS by activation of the mitogen-activated protein kinase (MAPK) pathway. Currently, BRAF mutations are divided into three classes on the basis of the mutation and biology and for drug development.5 Class I mutations involve the V600 amino acid, and result in activation of BRAF's kinase activity and constitutive activation of the MAPK pathway. The constitutive MAPK activation prevents BRAF dimerization, and the V600 mutant BRAF proteins signal constitutively as monomers.