European expert panel consensus on the clinical management of BRAFV600E-mutant metastatic colorectal cancer

Abstract

Metastatic colorectal cancer (mCRC) is a heterogenous disease caused by various genetic alterations. The BRAFV600E mutation occurs in approximately 8–12% of patients and is characterised by an aggressive clinical course and poor prognosis. Here we review the current knowledge on BRAFV600E-mutant mCRC and provide a series of consensus statements on its clinical management. The treatment landscape for BRAFV600E-mutant mCRC has changed greatly due to the emergence of molecular targeted therapies (including BRAF inhibitors) and immune checkpoint inhibitors. A scientific literature search identified available data on molecular testing, treatments, and clinical monitoring of patients with BRAFV600E-mutant mCRC. Consensus statements were discussed and developed by a European expert panel. This manuscript provides consensus management guidance for different clinical presentations of BRAFV600E-mutant mCRC and makes recommendations regarding treatment sequencing choices. To guide appropriate clinical management and treatment decisions for mCRC patients, tumour tissue analysis for DNA mismatch repair/microsatellite status and, at a minimum, KRAS, NRAS, and BRAF mutational status is mandatory at the time of diagnosis. Finally, we discuss the rapidly evolving treatment landscape for BRAFV600E-mutant mCRC and define priorities for the development of novel therapeutic strategies that are needed to improve patient outcomes.