BEACON CRC
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.
Overview
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.
- Median 9.3 vs 9.3 months with Encorafenib + binimetinib + cetuximab compared with Encorafenib + cetuximab; about 0 months longer for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- Other groups: Chemotherapy + cetuximab 5.9 months.
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- 27 vs 20 out of 100 had their tumour shrink with Encorafenib + binimetinib + cetuximab compared with Encorafenib + cetuximab; 7 more per 100.
- Roughly one extra person helped for every 14 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- Other groups: Chemotherapy + cetuximab 2 of 100.
- A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.
- These results apply to the people the trial enrolled: BRAF V600E-mutant metastatic colorectal cancer after one or two prior lines: encorafenib plus cetuximab with or without binimetinib, versus irinotecan-based chemotherapy plus cetuximab. People in a different situation may not see the same effect.
- The trial selected people by a biomarker (BRAF); the result should not be assumed for people whose cancer does not have it.
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 participants 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% |
Similar pages
not linked directly; found by shared links- TrialBREAKWATER
Shares Elena Élez, Scott Kopetz, Josep Tabernero, FOLFIRI (5-FU, leucovorin, irinotecan).
- Key paperBREAKWATER: encorafenib plus cetuximab with chemotherapy as first treatment for BRAF V600E-mutated colorectal cancer
Shares Elena Élez, Scott Kopetz, Josep Tabernero, Encorafenib.
- TrialA Study of Encorafenib Plus Cetuximab Taken Together With Pembrolizumab Compared to Pembrolizumab Alone in People With Previously Untreated Metastatic
Shares Encorafenib, BRAF V600E-mutant colorectal cancer, Cetuximab, Pfizer (incl. Seagen).
- PersonRyan B. Corcoran
Shares Encorafenib, Cetuximab, BRAF, EGFR.
- TrialCOLUMBUS
Shares Binimetinib, Encorafenib, BRAF, RAS / RAF / MEK / ERK (MAPK).
- TrialA Clinical Trial of Three Study Medicines (Encorafenib, Binimetinib, and Pembrolizumab) in Patients With Advanced or Metastatic Melanoma
Shares Binimetinib, Encorafenib, Pfizer (incl. Seagen).
- PairingBRAF inhibitor + MEK inhibitor
Shares Encorafenib, BRAF, RAS / RAF / MEK / ERK (MAPK), Colorectal cancer.
- PathwayMelanoma (KEGG map)
Shares Binimetinib, MEK1/2, Encorafenib, BRAF.