Encorafenib, Binimetinib and Cetuximab Combined Therapy for Patients with <i>BRAFV600E</i> Mutant Metastatic Colorectal Cancer
Sanne C.F.A. Huijberts, Robin M.J.M. van Geel, René Bernards, Jos H. Beijnen, Neeltje Steeghs
Abstract
Approximately 10–15% of colorectal cancers (CRCs) harbor an activating BRAF mutation, leading to tumor growth promotion by activation of the mitogen-activated protein kinases pathway. BRAFV600E mutations are prognostic for treatment failure after first-line systemic therapy in the metastatic setting. In contrast to the efficacy of combined BRAF and MEK inhibition in melanoma, BRAFV600E mutant CRC is intrinsically unresponsive due to upregulation of HER/EGFR. However, combining the EGFR inhibitor cetuximab, the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib improves overall survival. This review discusses the current treatment field for patients with BRAFV600E mutant metastatic CRC and summarizes the pharmacology, efficacy and safety of the novel doublet and triplet therapies consisting of encorafenib and cetuximab with or without binimetinib.