{"entity":{"id":"swog-s1406","kind":"trial","name":"SWOG S1406","aka":[],"tldr":"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.","status":"positive","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov NCT02164916","url":"https://clinicaltrials.gov/study/NCT02164916"},{"label":"SWOG S1406: irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (Journal of Clinical Oncology 2021)","url":"https://doi.org/10.1200/JCO.20.01994"}],"tags":[],"related":[],"cancers":["colorectal","braf-v600e-colorectal"],"sections":[],"technologies":["kinase-inhibitors","monoclonal-antibody"],"targets":["braf","egfr"],"drugs":["vemurafenib","cetuximab","irinotecan"],"companies":["swog"],"institutions":[],"pathways":[],"terms":[],"trials":["beacon-crc","breakwater"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02164916","phase":"2","setting":"Previously treated BRAF V600E-mutant metastatic colorectal cancer: irinotecan and cetuximab with or without vemurafenib","sponsor":"SWOG Cancer Research Network","result":"Progression-free survival hazard ratio 0.50 with vemurafenib added; response 17 against 4 percent.","yearReported":2021,"enrolled":106,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"hazard ratio","arms":[{"name":"Irinotecan, cetuximab and vemurafenib","value":0.5},{"name":"Irinotecan and cetuximab","value":1}],"hr":0.5,"p":"0.001","source":"https://doi.org/10.1200/JCO.20.01994"}],"replication":"BEACON CRC confirmed the principle with encorafenib and cetuximab in a phase 3 trial; BREAKWATER moved it to first line."},"route":"/trials/swog-s1406/","neighbours":{"cancer":[{"id":"braf-v600e-colorectal","kind":"cancer","name":"BRAF V600E-mutant colorectal cancer","route":"/cancers/braf-v600e-colorectal/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"technology":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"},{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"}],"drug":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},{"id":"encorafenib","kind":"drug","name":"Encorafenib","route":"/drugs/encorafenib/"},{"id":"irinotecan","kind":"drug","name":"Irinotecan (and liposomal irinotecan)","route":"/drugs/irinotecan/"},{"id":"vemurafenib","kind":"drug","name":"Vemurafenib","route":"/drugs/vemurafenib/"}],"company":[{"id":"swog","kind":"company","name":"SWOG Cancer Research Network","route":"/companies/swog/"}],"trial":[{"id":"beacon-crc","kind":"trial","name":"BEACON CRC","route":"/trials/beacon-crc/"},{"id":"breakwater","kind":"trial","name":"BREAKWATER","route":"/trials/breakwater/"}]}}