ABSTRACT
Introduction: BRAFV600E metastatic colorectal cancer (CRC) is an aggressive tumor subset with an approximate 8% incidence. In these patients, standard chemotherapy has limited efficacy, and the recent development of novel-targeted treatment regimens may significantly improve clinical outcome.
Area covered: This review provides an overview of available data regarding advances in the first–line treatment of BRAFV600E metastatic CRC including patient tumors with microsatellite instability. The implications of BRAFV600E in earlier stage CRC are also discussed.
Expert opinion: Recently, significant progress has been achieved in improving tumor response rates using a novel-targeted regimen in patients with BRAFV600E metastatic CRC. The implications of BRAFV600E in non-metastatic CRC are also becoming more evident and remains an area of ongoing investigation. The majority of CRCs with microsatellite instability high are sporadic and frequently harbor BRAFV600E. All patients with microsatellite instability high metastatic CRCs, irrespective of BRAFV600E, are candidates for immune checkpoint inhibitors. The optimal sequencing of treatment regimens for patients with BRAFV600E metastatic CRCs is an important area for future research.
Article highlights
Tumor mutation panel testing inclusive of RAS and BRAF should be performed on for all patients with metastatic colorectal cancers (mCRC) to guide treatment.
All patients with MSI-H/dMMR mCRC including those with BRAFV600E should be treated with immunotherapy given high tumor response rates that are shown to be durable.
BRAFV600E mCRC patients with favorable performance status may benefit from intensified treatment with FOLFOXIRI plus bevacizumab.
Targeted treatment with the combination of an EGFR inhibitor, a BRAF inhibitor, and a MEK inhibitor is a potent and effective treatment option for BRAFV600E mCRC.
Among patients with BRAFV600E mCRC, the optimal sequence of treatment and strategies to circumvent acquired drug resistance await further study.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.