BRAF V600E in Colorectal Cancer: Treatment Advances and Trials

BRAF V600E mutations occur in approximately 8-12% of colorectal cancers (CRC) and are associated with a more aggressive disease course. However, recent advances in targeted therapy are changing outcomes for these patients.

What is BRAF V600E?

BRAF is a gene that produces a protein involved in cell growth signaling. The V600E mutation causes this protein to be constantly active, leading to uncontrolled cell growth. In colorectal cancer, this mutation is often associated with:

• Right-sided tumors
• Older age at diagnosis
• Female predominance
• Often co-occurring with MSI-High status

Standard Treatment Approach

Unlike BRAF V600E in melanoma, single-agent BRAF inhibitors (like vemurafenib) are not effective in colorectal cancer due to feedback activation of EGFR. The current standard approach combines:

Encorafenib + Cetuximab (BEACON Regimen)

The BEACON trial established this combination as standard of care for previously treated BRAF V600E metastatic CRC:

• Encorafenib: BRAF inhibitor
• Cetuximab: EGFR inhibitor
• Significantly improved overall survival vs. standard chemotherapy
• FDA approved in 2020

Current Clinical Trials

Research is ongoing to improve outcomes further:

• First-line combinations: Testing BRAF-targeted therapy earlier in treatment
• Immunotherapy combinations: For MSI-H/BRAF V600E tumors
• Novel BRAF inhibitors: Next-generation compounds with improved activity

Testing Recommendations

All patients with metastatic colorectal cancer should have BRAF testing at diagnosis. This can be done through:

• Next-generation sequencing (NGS) panels
• PCR-based single-gene testing
• Immunohistochemistry (as a screening tool)

Find Matching Trials

Use ClinicalMatch.ai to search for trials specifically recruiting BRAF V600E colorectal cancer patients.