Management of BRAF-mutant metastatic colorectal cancer: a review of treatment options and evidence-based guidelines.
Ann Oncol
; 32(8): 959-967, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-33836264
ABSTRACT
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 â¼10% 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 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) 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 Binimetinib, Encorafenib, And Cetuximab cOmbiNed to treat BRAF-mutant ColoRectal Cancer (BEACON CRC) 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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
/
Proteínas Proto-Oncogênicas B-raf
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article