Approximatively 8-15% of patients with metastatic colorectal cancer (mCRC) harbor mutation in BRAF gene. Recent advances in molecular biology enabled a better knowledge of the molecular heterogeneity within BRAF mutant (BRAF) CRCs, including high rate of overlapping with MSI-H status and detection of non-V600E mutations related to more favorable behavior. Treatment armamentarium has been rapidly growing in this subgroup and includes targeted combinations and immunotherapy for concomitant MSI-H patients, thereby making BRAF mCRC an innovative model for precision oncology. Nevertheless, duration of responses to targeted strategies remains unsatisfactory due to the development of secondary resistance, which is currently the field of major clinical research on BRAF mCRC. This review explores the molecular, clinical and therapeutic landscape of BRAF mCRC as well as an update on current treatment strategies and future perspectives in light of the heterogeneity of BRAF-mutated disease. Furthermore, a novel treatment algorithm for BRAF mCRC will be proposed.
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http://dx.doi.org/10.1016/j.critrevonc.2022.103657 | DOI Listing |
Am J Cancer Res
December 2024
Graduate Institute of Oncology, National Taiwan University College of Medicine Taipei 10051, Taiwan.
The combination of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAb) and doublet chemotherapy is the standard first-line treatment for patients with wild-type metastatic colorectal cancer (mCRC). Some patients may require secondary resection after first-line treatment. However, it remains unclear whether targeted therapy should be continued after liver resection.
View Article and Find Full Text PDFClin Colorectal Cancer
December 2024
Austin Hospital, Heidelberg, Victoria, Australia.
Background: Panitumumab (pan) plus chemotherapy is a preferred first-line therapy for unresectable RAS and BRAF wild type metastatic colorectal cancer (mCRC). Older patients may not be suitable for combination regimens. We investigated 2 lower intensity pan-containing regimens.
View Article and Find Full Text PDFTher Adv Med Oncol
January 2025
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 67, Pisa 56126, Italy.
Background: Encorafenib plus cetuximab (EC) is the standard of care for pre-treated mutated metastatic colorectal cancer (mCRC). Depth of response (DpR) and early tumour shrinkage (ETS) previously showed a strong correlation with survival outcomes of first-line chemotherapy ± biological agents.
Objectives: We aimed to assess potential predictors of primary resistance to EC ± binimetinib (B) and relationships of DpR/ETS with survival outcomes and clinical characteristics.
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.
Purpose: overexpression/amplification in wild-type (WT) metastatic colorectal cancer (mCRC; human epidermal growth factor receptor 2 [HER2]-positive mCRC) appears to be associated with limited benefit from anti-EGFR antibodies and promising responses to dual-HER2 inhibition; however, comparative efficacy has not been investigated. We conducted a randomized phase II trial to evaluate efficacy and safety of dual-HER2 inhibition against standard-of-care anti-EGFR antibody-based therapy as second/third-line treatment in HER2-positive mCRC.
Methods: Patients with -WT mCRC after central confirmation of HER2 positivity (immunohistochemistry 3+ or 2+ and in situ hybridization amplified [HER2/CEP17 ratio >2.
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