Metastatic colorectal cancer (mCRC) is a heterogenous disease caused by various genetic alterations. The BRAF mutation occurs in approximately 8-12% of patients and is characterised by an aggressive clinical course and poor prognosis. Here we review the current knowledge on BRAF-mutant mCRC and provide a series of consensus statements on its clinical management. The treatment landscape for BRAF-mutant mCRC has changed greatly due to the emergence of molecular targeted therapies (including BRAF inhibitors) and immune checkpoint inhibitors. A scientific literature search identified available data on molecular testing, treatments, and clinical monitoring of patients with BRAF-mutant mCRC. Consensus statements were discussed and developed by a European expert panel. This manuscript provides consensus management guidance for different clinical presentations of BRAF-mutant mCRC and makes recommendations regarding treatment sequencing choices. To guide appropriate clinical management and treatment decisions for mCRC patients, tumour tissue analysis for DNA mismatch repair/microsatellite status and, at a minimum, KRAS, NRAS, and BRAF mutational status is mandatory at the time of diagnosis. Finally, we discuss the rapidly evolving treatment landscape for BRAF-mutant mCRC and define priorities for the development of novel therapeutic strategies that are needed to improve patient outcomes.
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http://dx.doi.org/10.1016/j.ctrv.2023.102541 | DOI Listing |
Cancers (Basel)
December 2024
Medical Oncology, Vall d'Hebron University Hospital, 08035 Barcelona, Spain.
Background: For patients with refractory metastatic colorectal cancer (mCRC), trifluridine/tipiracil (FTD-TPI) has been associated with a significant improvement in overall survival (OS). However, data are lacking regarding the activity of FTD-TPI in patients with -mutated mCRC.
Methods: This retrospective, multicenter, international cohort included patients with -mutated mCRC treated with FTD-TPI in a real-life setting in Spain and Italy.
In Vivo
December 2024
Medical Oncology Unit, Policlinico, University of Palermo, Palermo, Italy.
Patients affected by metastatic carcinoma of the colon/rectum (mCRC) harboring mutations in the BRAF gene (MBRAF) respond poorly to conventional therapy and have a prognosis worse than that of patients without mutations. Despite the promising outcomes of targeted therapy utilizing multi-targeted inhibition of the mitogen-activated protein kinase (MAPK) signaling system, the therapeutic efficacy, especially for the microsatellite stable/DNA proficient mismatch repair (MSS/PMMR) subtype, remains inadequate. Patients with MBRAF/mCRC and high microsatellite instability or DNA deficient mismatch repair (MSI-H/DMMR) exhibit a substantial tumor mutation burden, suggesting a high probability of response to immunotherapy.
View Article and Find Full Text PDFESMO Open
September 2024
Department of Medicine III and Comprehensive Cancer Center, University Hospital, LMU Munich, Munich; German Cancer Consortium (DKTK), DKFZ, Heidelberg, Munich.
Background: Primary tumor (PT) sidedness is an established prognostic marker in metastatic colorectal cancer (mCRC) and has a predictive impact on the efficacy of anti-epidermal growth factor receptor (anti-EGFR) antibody [monoclonal antibody (mAb)] in patients with RAS wild-type mCRC. This investigation focuses on patients with BRAF-mutated (BRAFmt) mCRC and examines the efficacy of anti-EGFR mAbs in relation to primary tumor sidedness (PTS).
Patient And Methods: This pooled analysis was carried out using individual patient data from five randomized studies in the first-line setting of mCRC.
J Anus Rectum Colon
April 2024
Division of Lower GI Surgery, Department of Gastroenterological Surgery, Hyogo Medical University, Nishinomiya, Japan.
Background: Spatial and temporal heterogeneities of RAS and other molecular genes should be considered in the treatment of metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs); acquired RAS mutation is sometimes observed at disease progression of treatment with the anti-EGFR mAb. At the same time, discrepancy of RAS status from tissues and circulating tumor DNA (ctDNA) in the same patient is sometimes observed. Based on this, we commenced two observational studies to clarify these heterogeneities of RAS and BRAF in mCRC, using next generation sequencing from liquid biopsy.
View Article and Find Full Text PDFCancers (Basel)
March 2024
Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
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