{"entity":{"id":"paper-cremolini-tribe-folfoxiri-bevacizumab-lancet-oncol-2015","kind":"paper","name":"FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of TRIBE","aka":[],"tldr":"Giving all three chemotherapy drugs at once rather than two added four months of life, and worked whatever the RAS or BRAF status. It is the most intensive first-line option for patients fit enough to take it.","summary":"TRIBE was an open-label phase 3 randomised study in patients with unresectable metastatic colorectal cancer recruited from 34 Italian oncology units, aged 18 to 70 with ECOG performance status of 2 or less, or 71 to 75 with performance status 0. Patients were randomised 1:1 to FOLFIRI plus bevacizumab or FOLFOXIRI plus bevacizumab; tissue for RAS and BRAF status was collected centrally. This updated analysis reports overall survival, a secondary endpoint, and treatment efficacy in the molecular subgroups.\n\nBetween July 2008 and May 2011, 508 patients were randomised, and the trial closed on 30 November 2014.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2015","url":"https://doi.org/10.1016/S1470-2045(15)00122-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26338525/"}],"tags":["colorectal-evidence"],"related":["paper-kopetz-beacon-encorafenib-braf-colorectal-nejm-2019","paper-heinemann-fire-3-cetuximab-vs-bevacizumab-lancet-oncol-2014"],"cancers":["colorectal","braf-v600e-colorectal"],"sections":["chemotherapy"],"technologies":["cytotoxic-chemotherapy","antiangiogenic"],"targets":["kras","braf","vegf"],"drugs":["folfirinox","folfiri","bevacizumab","oxaliplatin","irinotecan","fluorouracil"],"companies":[],"institutions":[],"pathways":[],"terms":["folfox-family"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2015,"doi":"10.1016/S1470-2045(15)00122-9","pmid":"26338525","authors":"Cremolini C, Loupakis F, Antoniotti C, et al.","paperType":"rct","findings":["At a median 48.1 months, median overall survival 29.8 months (95 percent CI 26.0 to 34.3) with FOLFOXIRI plus bevacizumab against 25.8 months (22.5 to 29.1): hazard ratio 0.80 (0.65 to 0.98, p=0.03).","Median overall survival by subgroup: 37.1 months in RAS and BRAF wild-type disease, 25.6 months in RAS-mutant disease (hazard ratio 1.49) and 13.4 months in BRAF-mutant disease (hazard ratio 2.79); likelihood-ratio test p<0.0001.","Treatment effect did not differ significantly across molecular subgroups (p for interaction 0.52)."],"whatItMeans":"The triplet is the option for fit patients who need a response, particularly in BRAF-mutant and right-sided disease where the EGFR antibody route is closed; it also quantified how much worse BRAF-mutant disease was before BEACON and BREAKWATER.","caveats":["Overall survival was a secondary endpoint in an updated analysis.","Eligibility was restricted by age and performance status; the triplet is not deliverable to most patients with metastatic colorectal cancer.","Italian centres only, and the control arm did not include an EGFR antibody."],"changedPractice":true,"participants":508},"route":"/key-papers/paper-cremolini-tribe-folfoxiri-bevacizumab-lancet-oncol-2015/","neighbours":{"paper":[{"id":"paper-kopetz-beacon-encorafenib-braf-colorectal-nejm-2019","kind":"paper","name":"Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer (BEACON CRC)","route":"/key-papers/paper-kopetz-beacon-encorafenib-braf-colorectal-nejm-2019/"},{"id":"paper-heinemann-fire-3-cetuximab-vs-bevacizumab-lancet-oncol-2014","kind":"paper","name":"FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3)","route":"/key-papers/paper-heinemann-fire-3-cetuximab-vs-bevacizumab-lancet-oncol-2014/"}],"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/"}],"section":[{"id":"chemotherapy","kind":"section","name":"Chemotherapy","route":"/fronts/chemotherapy/"}],"technology":[{"id":"antiangiogenic","kind":"technology","name":"Anti-angiogenic therapy","route":"/technologies/antiangiogenic/"},{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"vegf","kind":"target","name":"VEGF / VEGFR","route":"/targets/vegf/"}],"drug":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"},{"id":"folfiri","kind":"drug","name":"FOLFIRI (5-FU, leucovorin, irinotecan)","route":"/drugs/folfiri/"},{"id":"folfirinox","kind":"drug","name":"FOLFIRINOX / mFOLFIRINOX","route":"/drugs/folfirinox/"},{"id":"irinotecan","kind":"drug","name":"Irinotecan (and liposomal irinotecan)","route":"/drugs/irinotecan/"},{"id":"oxaliplatin","kind":"drug","name":"Oxaliplatin","route":"/drugs/oxaliplatin/"}],"term":[{"id":"folfox-family","kind":"term","name":"FOLFOX, FOLFIRI, FOLFIRINOX and CAPOX","route":"/terms/folfox-family/"}],"bottleneck":[{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"journal":[{"id":"lancet-oncology","kind":"journal","name":"The Lancet Oncology","route":"/journals/lancet-oncology/"}]}}