BACKGROUND Colorectal cancer (CRC) is still a leading cause of cancer-related deaths in the United States and worldwide, despite recent improvements in cancer management. CRC, like many malignancies, is a heterogeneous disease, with subtypes characterized by genetic alterations. One common mutation in CRC is in the BRAF gene (most commonly V600E substitution). This occurs in approximately 10% of patients with metastatic CRC (mCRC) and is a marker of poor prognosis. DESIGN Herein, we review the clinical and translational literature on the role of the BRAF V600E mutation in the pathogenesis of mCRC, its mechanisms as a prognostic marker and its potential utility as a predictive marker of treatment response. We then summarize the current evidence-based recommendations for management of BRAF V600E-mutated mCRC, with a focus on recent clinical research advances in this setting. RESULTS The current standard therapies for first-line treatment of BRAF-mutated mCRC are chemotherapy with bevacizumab as well as FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab in patients with a good performance status. Combination strategies involving mitogen-activated protein kinase (MAPK) pathway blockade have shown promising results for the treatment of patients with BRAF V600E-mutated mCRC. The BEACON study represents the largest study in this population to date and has given strong clinical evidence to support BRAF and epidermal growth factor receptor inhibition with the combination of encorafenib plus cetuximab. CONCLUSIONS The treatment of BRAF-mutated mCRC has evolved rapidly over the last several years. Recently, combination strategies involving MAPK pathway blockade have shown promising results in BRAF V600E-mutated mCRC, and other potential targets continue to be explored. In addition, a greater understanding of the role of BRAF V600E mutation in the pathogenesis of CRC should also continue to fuel advances in the management of patients with mCRC harboring this genetic aberration.
Management of BRAF-mutant metastatic colorectal cancer: a review of treatment options and evidence-based guidelines.
A. Grothey,M. Fakih,J. Tabernero
Published 2021 in Annals of Oncology
ABSTRACT
PUBLICATION RECORD
- Publication year
2021
- Venue
Annals of Oncology
- Publication date
2021-04-06
- Fields of study
Medicine
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
CONCEPTS
- beacon study
The major clinical trial cited here as the largest study in this patient population.
- braf v600e mutation
A specific activating substitution in the BRAF gene discussed as the main mutation of interest in metastatic colorectal cancer.
Aliases: BRAF V600E
- chemotherapy with bevacizumab
A first-line treatment approach combining standard cytotoxic chemotherapy with the anti-VEGF antibody bevacizumab.
- encorafenib plus cetuximab
The targeted drug combination pairing the BRAF inhibitor encorafenib with the EGFR inhibitor cetuximab.
- folfoxiri plus bevacizumab
A triplet chemotherapy regimen consisting of 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan given with bevacizumab.
- mapk pathway blockade
The mitogen-activated protein kinase signaling cascade targeted by combination strategies discussed in the review.
Aliases: MAPK
- metastatic colorectal cancer
Colorectal cancer that has spread beyond the primary tumor site and is the disease setting addressed in the review.
Aliases: mCRC
REFERENCES
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