Advances in the therapy of BRAF^V600E metastatic colorectal cancer

ABSTRACT

Introduction: BRAF^V600E 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 BRAF^V600E metastatic CRC including patient tumors with microsatellite instability. The implications of BRAF^V600E 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 BRAF^V600E metastatic CRC. The implications of BRAF^V600E 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 BRAF^V600E. All patients with microsatellite instability high metastatic CRCs, irrespective of BRAF^V600E, are candidates for immune checkpoint inhibitors. The optimal sequencing of treatment regimens for patients with BRAF^V600E metastatic CRCs is an important area for future research.

KEYWORDS:

• BRAF^V600E
• colorectal cancer
• targeted treatment
• microsatellite instability
• circulating tumor DNA

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 BRAF^V600E should be treated with immunotherapy given high tumor response rates that are shown to be durable.

• BRAF^V600E 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 BRAF^V600E mCRC.

• Among patients with BRAF^V600E 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.

Additional information

Funding

This paper was not funded.