# SWOG S1406

Source: https://onco.cc/trials/swog-s1406/  
OnCo record `swog-s1406` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The trial that explained why BRAF drugs alone fail in bowel cancer: blocking BRAF wakes up EGFR, so both must be blocked at once.

## Summary

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.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-24
- Registry id: NCT02164916
- Phase: 2
- Setting: Previously treated BRAF V600E-mutant metastatic colorectal cancer: irinotecan and cetuximab with or without vemurafenib
- Sponsor: SWOG Cancer Research Network
- Enrolled: 106
- Result: Progression-free survival hazard ratio 0.50 with vemurafenib added; response 17 against 4 percent.
- Outcomes: Progression-free survival: Irinotecan, cetuximab and vemurafenib 0.5 hazard ratio vs Irinotecan and cetuximab 1 hazard ratio, HR 0.5
- Replication: BEACON CRC confirmed the principle with encorafenib and cetuximab in a phase 3 trial; BREAKWATER moved it to first line.

## Sources

- ClinicalTrials.gov NCT02164916: https://clinicaltrials.gov/study/NCT02164916
- SWOG S1406: irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (Journal of Clinical Oncology 2021): https://doi.org/10.1200/JCO.20.01994

## Connected records

- cancers: [BRAF V600E-mutant colorectal cancer](https://onco.cc/cancers/braf-v600e-colorectal/), [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- technologies: [Monoclonal antibodies](https://onco.cc/technologies/monoclonal-antibody/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [BRAF](https://onco.cc/targets/braf/), [EGFR](https://onco.cc/targets/egfr/)
- drugs: [Cetuximab](https://onco.cc/drugs/cetuximab/), [Encorafenib](https://onco.cc/drugs/encorafenib/), [Irinotecan (and liposomal irinotecan)](https://onco.cc/drugs/irinotecan/), [Vemurafenib](https://onco.cc/drugs/vemurafenib/)
- companies: [SWOG Cancer Research Network](https://onco.cc/companies/swog/)
- trials: [BEACON CRC](https://onco.cc/trials/beacon-crc/), [BREAKWATER](https://onco.cc/trials/breakwater/)

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