Loading
BEACON was the first trial to show that blocking BRAF works in bowel cancer once the escape route through EGFR is blocked too: encorafenib with cetuximab lengthened life and shrank ten times as many tumours as chemotherapy.
BEACON CRC randomised 665 patients with BRAF V600E-mutant metastatic colorectal cancer that had progressed after one or two regimens to encorafenib, binimetinib and cetuximab (triplet), encorafenib and cetuximab (doublet), or investigator-choice irinotecan or FOLFIRI with cetuximab. Earlier BRAF inhibitor monotherapy had failed in this disease because loss of BRAF signalling releases feedback activation of EGFR, which the antibody blocks.
In the updated analysis median overall survival was 9.3 months with the triplet and 9.3 months with the doublet against 5.9 months with control; confirmed response rates were 27 percent, 20 percent and 2 percent. The MEK inhibitor added toxicity without a survival gain, so the doublet became the regimen taken forward.
The FDA approved encorafenib with cetuximab for previously treated BRAF V600E colorectal cancer in April 2020, the first targeted therapy for this subtype, and BREAKWATER then moved the doublet, with FOLFOX, into first-line treatment.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
665 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survival (updated analysis)primary | Encorafenib + binimetinib + cetuximab | 224 | 9.3 months | - | - | link |
| Encorafenib + cetuximab | 220 | 9.3 months | ||||
| Chemotherapy + cetuximab | 221 | 5.9 months | ||||
| Confirmed objective response rate | Encorafenib + binimetinib + cetuximab | 224 | 27% | - | - | link |
| Encorafenib + cetuximab | 220 | 20% | ||||
| Chemotherapy + cetuximab | 221 | 2% |
This is the European standard the UK and NHS page for colorectal cancer is compared against; NICE NG151 covers the same ground for England with a narrower set of funded drugs.
One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
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 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.
It fixes the metastatic prevalence figures every subsequent trial design has used, and it separates two biomarkers that travel together: BRAF, not mismatch repair deficiency, is what makes the prognosis bad.
Shares Elena Élez, SWOG S1406, Non-V600 BRAF mutations define a clinically distinct molecular subtype of metastatic colorectal cancer, Scott Kopetz.
Shares Elena Élez, Scott Kopetz, Josep Tabernero, Encorafenib.
Shares Encorafenib, BRAF V600E-mutant colorectal cancer, Cetuximab, Pfizer (incl. Seagen).
Shares Non-V600 BRAF mutations define a clinically distinct molecular subtype of metastatic colorectal cancer, Mismatch repair status and BRAF mutation status in metastatic colorectal cancer: a pooled analysis of the CAIRO, CAIRO2, COIN and FOCUS studies, Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer (BEACON CRC), Binimetinib.
Shares Irinotecan (and liposomal irinotecan), FOLFIRI (5-FU, leucovorin, irinotecan), Cetuximab, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation.
Shares Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer (BEACON CRC), BRAF V600E-mutant colorectal cancer, Irinotecan (and liposomal irinotecan), FOLFIRI (5-FU, leucovorin, irinotecan).
Shares Encorafenib, BRAF V600E-mutant colorectal cancer, Cetuximab, Monoclonal antibodies.
Shares Irinotecan (and liposomal irinotecan), FOLFIRI (5-FU, leucovorin, irinotecan), Cetuximab, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation.