# 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

Source: https://onco.cc/key-papers/paper-cremolini-tribe-folfoxiri-bevacizumab-lancet-oncol-2015/  
OnCo record `paper-cremolini-tribe-folfoxiri-bevacizumab-lancet-oncol-2015` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

Between July 2008 and May 2011, 508 patients were randomised, and the trial closed on 30 November 2014.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: colorectal-evidence
- Journal: The Lancet Oncology
- Year: 2015
- DOI: 10.1016/S1470-2045(15)00122-9
- Authors: Cremolini C, Loupakis F, Antoniotti C, et al.
- 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).
- What it means: 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.

## Sources

- Lancet Oncol 2015: https://doi.org/10.1016/S1470-2045(15)00122-9
- PubMed: https://pubmed.ncbi.nlm.nih.gov/26338525/

## Connected records

- key papers: [Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer (BEACON CRC)](https://onco.cc/key-papers/paper-kopetz-beacon-encorafenib-braf-colorectal-nejm-2019/), [FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3)](https://onco.cc/key-papers/paper-heinemann-fire-3-cetuximab-vs-bevacizumab-lancet-oncol-2014/)
- cancers: [BRAF V600E-mutant colorectal cancer](https://onco.cc/cancers/braf-v600e-colorectal/), [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- fronts: [Chemotherapy](https://onco.cc/fronts/chemotherapy/)
- technologies: [Anti-angiogenic therapy](https://onco.cc/technologies/antiangiogenic/), [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/)
- targets: [BRAF](https://onco.cc/targets/braf/), [KRAS](https://onco.cc/targets/kras/), [VEGF / VEGFR](https://onco.cc/targets/vegf/)
- drugs: [Bevacizumab](https://onco.cc/drugs/bevacizumab/), [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [FOLFIRI (5-FU, leucovorin, irinotecan)](https://onco.cc/drugs/folfiri/), [FOLFIRINOX / mFOLFIRINOX](https://onco.cc/drugs/folfirinox/), [Irinotecan (and liposomal irinotecan)](https://onco.cc/drugs/irinotecan/), [Oxaliplatin](https://onco.cc/drugs/oxaliplatin/)
- terms: [FOLFOX, FOLFIRI, FOLFIRINOX and CAPOX](https://onco.cc/terms/folfox-family/)
- bottlenecks: [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)

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