BREAKWATER
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 was previously a near-death sentence with median OS around a year.
- Median 12.8 vs 7.1 months with Encorafenib + cetuximab + mFOLFOX6 compared with Chemotherapy ± bevacizumab; about 5.7 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.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- Median 30.3 vs 15.1 months with Encorafenib + cetuximab + mFOLFOX6 compared with Chemotherapy ± bevacizumab; about 15.2 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.
- Put another way, the treated group had about 51 percent lower chance of the event at any given time (hazard ratio 0.49).
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- The treated group had about 56 percent lower chance of the event at any given time (hazard ratio 0.44).
- The absolute difference, how many more people out of 100 were helped, is not reported here.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- These results apply to the people the trial enrolled: First-line BRAF V600E-mutant metastatic colorectal cancer: encorafenib + cetuximab + mFOLFOX6 (or FOLFIRI) vs chemotherapy ± bevacizumab. 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.
| 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 | — | — |
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