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Led BEACON and BREAKWATER, the trials that gave BRAF-mutant colorectal cancer its first targeted therapies.
Scott Kopetz led BEACON CRC, which established encorafenib plus cetuximab for previously treated BRAF V600E colorectal cancer, and BREAKWATER, which moved the combination with chemotherapy into first line with a large survival gain. He co-developed the consensus molecular subtypes of colorectal cancer and leads ctDNA-guided adjuvant trials in the NCI cooperative groups.
| Title | Journal | Year |
|---|---|---|
| Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer (BEACON) | NEJM | 2019 |
| The consensus molecular subtypes of colorectal cancer | Nature Medicine | 2015 |
| Encorafenib, cetuximab, and chemotherapy in BRAF-mutated colorectal cancer (BREAKWATER) | NEJM | 2025 |
| BREAKWATER: encorafenib plus cetuximab with chemotherapy as first treatment for BRAF V600E-mutated colorectal cancer | New England Journal of Medicine | 2025 |
Patients with newly diagnosed metastatic colorectal cancer whose tumour carries a BRAF V600E mutation, which is about 8-12% of cases, should now be offered encorafenib and cetuximab together with FOLFOX from the start rather than after chemotherapy fails; median survival has roughly doubled to about two and a half years. BRAF testing at diagnosis is therefore essential, alongside RAS and mismatch repair testing. The regimen is more toxic than chemotherapy alone.
Encorafenib with cetuximab became the standard second-line treatment for BRAF V600E disease, and the platform BREAKWATER later moved into first line with chemotherapy added, doubling survival again.
It is the reference for what a colorectal molecular report must contain, and the document that turned extended RAS from a trial finding into a requirement.
It gave the second PD-1 antibody a colorectal indication in mismatch repair deficient disease and, with the ipilimumab cohort that followed, set up CheckMate 8HW and the first-line combination.
It stops a BRAF-mutant report being read as one uniform outlook, and it separates the class II and III mutations, which signal differently and are not covered by the encorafenib plus cetuximab label, from V600E.
Shares BREAKWATER, BEACON CRC, BREAKWATER: encorafenib plus cetuximab with chemotherapy as first treatment for BRAF V600E-mutated colorectal cancer, Encorafenib.
Shares BRAF V600E-mutant colorectal cancer, Colorectal cancer and the tags colorectal, targeted-therapy.
Shares BREAKWATER, BEACON CRC, Encorafenib, BRAF V600E-mutant colorectal cancer.
Shares BREAKWATER, BEACON CRC, Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer (BEACON CRC), BREAKWATER: encorafenib plus cetuximab with chemotherapy as first treatment for BRAF V600E-mutated colorectal cancer.
Shares Colorectal cancer and the tags colorectal, targeted-therapy.
Shares Colorectal cancer and the tags colorectal, targeted-therapy.
Shares Colorectal cancer and the tags colorectal, targeted-therapy.
Shares Non-V600 BRAF mutations define a clinically distinct molecular subtype of metastatic colorectal cancer, Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer (BEACON CRC), BREAKWATER: encorafenib plus cetuximab with chemotherapy as first treatment for BRAF V600E-mutated colorectal cancer, Encorafenib and the tag braf.