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The trial that explained why BRAF drugs alone fail in bowel cancer: blocking BRAF wakes up EGFR, so both must be blocked at once.
SWOG S1406 randomised 106 patients with BRAF V600E-mutant metastatic colorectal cancer treated with one or two previous regimens to irinotecan and cetuximab with or without vemurafenib 960 mg twice daily. Progression-free survival, the primary endpoint, improved with vemurafenib (hazard ratio 0.50, p=0.001), the response rate was 17 against 4 percent (p=0.05) and disease control 65 against 21 percent. Blockade of BRAF V600E alone causes feedback upregulation of EGFR in colorectal cancer, which cetuximab impedes; that mechanism, first shown in the laboratory, is what S1406 confirmed in patients and what BEACON CRC then turned into an approved doublet with encorafenib.
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.
106 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survivalprimary | Irinotecan, cetuximab and vemurafenib | - | 0.5 hazard ratio | 0.5 | 0.001 | link |
| Irinotecan and cetuximab | - | 1 hazard ratio |
Shares BREAKWATER, BEACON CRC, Encorafenib, BRAF V600E-mutant colorectal cancer.
Shares BREAKWATER, BEACON CRC, Encorafenib, BRAF V600E-mutant colorectal cancer.
Shares BEACON CRC, Encorafenib, BRAF V600E-mutant colorectal cancer, BRAF.
Shares Encorafenib, BRAF V600E-mutant colorectal cancer, Cetuximab, Monoclonal antibodies.
Shares BREAKWATER, BEACON CRC, Encorafenib, BRAF V600E-mutant colorectal cancer.
Shares Encorafenib, BRAF V600E-mutant colorectal cancer, Cetuximab, Monoclonal antibodies.
Shares BREAKWATER, BEACON CRC, Encorafenib, BRAF V600E-mutant colorectal cancer.
Shares Encorafenib, BRAF, Cetuximab, EGFR.