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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
BRAF V600E bowel cancer carries the same mutation as many melanomas, but BRAF drugs alone did nothing here because the tumour re-routes its growth signal through EGFR. Blocking both with encorafenib and cetuximab, now given with chemotherapy from the start, has doubled survival in a subtype that used to be the worst.
BRAF V600E locks the RAS-MAPK pathway on, and in colorectal cancer it arises in the serrated pathway with CpG island methylation; about a third of localised BRAF-mutant tumours are also mismatch-repair deficient, in which case the immunotherapy of that subtype applies and the outlook is good. Microsatellite-stable BRAF V600E disease is different: it is often right-sided, presents with peritoneal and nodal spread, responds poorly to chemotherapy, and anti-EGFR antibodies alone do not work. Non-V600 BRAF mutations, about 2 percent of cancers, behave as a separate and less aggressive group.
Single-agent vemurafenib failed in 2011 because inhibiting BRAF in bowel cells releases feedback activation of EGFR; blocking both proved the answer. BEACON CRC (2019) randomised 665 previously treated patients to encorafenib and cetuximab with or without binimetinib against chemotherapy plus cetuximab: median survival was 9.3 months with either targeted regimen against 5.9 months, response rates were 20 to 27 percent against 2 percent, and the FDA approved encorafenib with cetuximab in April 2020. BREAKWATER (2024 to 2025) then moved the doublet into first line with mFOLFOX6: the response rate was 61 percent against 40 percent for chemotherapy and median survival 30.3 months against 15.1 months, which brought accelerated approval in December 2024 and full approval in 2026.
| Setting | Approach | Guideline |
|---|---|---|
| Metastatic, microsatellite-stable, first line | Encorafenib plus cetuximab plus mFOLFOX6 (BREAKWATER); encorafenib plus cetuximab alone for patients unfit for chemotherapy. | not mapped |
| Metastatic, previously treated | Encorafenib plus cetuximab (BEACON CRC) if not already given; then trifluridine-tipiracil with bevacizumab, fruquintinib or regorafenib. | not mapped |
| Metastatic, mismatch-repair deficient | Checkpoint blockade first (pembrolizumab, or nivolumab plus ipilimumab); BRAF-targeted therapy at progression. | not mapped |
| Localised | Surgery and stage-based adjuvant FOLFOX or CAPOX as for colorectal cancer; BRAF status does not yet change adjuvant treatment outside trials. | not mapped |