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Doubled survival, from about 15 to about 30 months, in the worst-prognosis genetic subtype of bowel cancer by adding two targeted drugs to first-line chemotherapy.
EC + mFOLFOX6: PFS 12.8 vs 7.1 months; OS 30.3 vs 15.1 months (HR 0.49; ASCO 2025 LBA3500). The FOLFIRI cohort (ASCO 2026 LBA3503) showed PFS HR 0.44 and OS HR 0.56. FDA accelerated approval December 2024 (first under Project FrontRunner), converted toward full approval in 2026. BRAF V600E disease previously had a median overall survival of around a year.
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.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survival (EC + mFOLFOX6) | Encorafenib + cetuximab + mFOLFOX6 | - | 30.3 months | 0.49 | - | link |
| Chemotherapy ± bevacizumab | - | 15.1 months | ||||
| Progression-free survival (EC + mFOLFOX6)primary | Encorafenib + cetuximab + mFOLFOX6 | - | 12.8 months | - | - | link |
| Chemotherapy ± bevacizumab | - | 7.1 months | ||||
| Progression-free survival (EC + FOLFIRI cohort) | Encorafenib + cetuximab + FOLFIRI | - | - | 0.44 | - | link |
| Chemotherapy ± bevacizumab | - | - |
This is the paper Europe PMC returns for registry id NCT04607421 with the most citations, so it is the natural first reading for anyone following the BREAKWATER trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically 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.
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 Encorafenib, Cetuximab, BRAF, EGFR.
Shares 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, FOLFOX (5-FU, leucovorin, oxaliplatin).
Shares Encorafenib, BRAF V600E-mutant colorectal cancer, Cetuximab, Small-molecule kinase inhibitors.
Shares Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer (BEACON CRC), BRAF V600E-mutant colorectal cancer, FOLFIRI (5-FU, leucovorin, irinotecan), BRAF.
Shares Josep Tabernero, BRAF, 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, FOLFOX (5-FU, leucovorin, oxaliplatin).