# Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in KRAS wild-type advanced or metastatic colorectal cancer (CALGB/SWOG 80405)

Source: https://onco.cc/key-papers/paper-venook-calgb-80405-cetuximab-vs-bevacizumab-jama-2017/  
OnCo record `paper-venook-calgb-80405-cetuximab-vs-bevacizumab-jama-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The American head-to-head of the same two antibodies, in 1,137 patients, found no difference: 30.0 against 29.0 months. Read next to FIRE-3, it is why sidedness had to be invoked.

## Summary

Venook, Niedzwiecki, Lenz and colleagues enrolled previously untreated patients aged 18 or older with advanced or metastatic KRAS wild-type colorectal cancer at community and academic centres across the National Clinical Trials Network in the United States and Canada between November 2005 and March 2012. Patients chose mFOLFOX6 or FOLFIRI as their chemotherapy and were randomised to cetuximab (578) or bevacizumab (559). The primary endpoint was overall survival; last follow-up was December 2015.

Of 1,137 patients (median age 59; 440, 39 percent, women), 1,074 (94 percent) met eligibility criteria, and 82 percent had experienced disease progression by the data cut.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: colorectal-evidence
- Journal: JAMA
- Year: 2017
- DOI: 10.1001/jama.2017.7105
- Authors: Venook AP, Niedzwiecki D, Lenz HJ, et al.
- Findings: Median overall survival 30.0 months with cetuximab-chemotherapy against 29.0 months with bevacizumab-chemotherapy: stratified hazard ratio 0.88 (95 percent CI 0.77 to 1.01, p=0.08).; Median progression-free survival 10.5 against 10.6 months (0.95, 0.84 to 1.08, p=0.45).; Response rates 59.6 against 55.2 percent (difference 4.4 percent, p=0.13).; Median follow-up for the 263 surviving patients was 47.4 months.
- What it means: The negative counterweight to FIRE-3. The two trials are reconciled only by primary tumour side, which is why the sidedness analysis rather than either trial is what guidelines now cite.
- Caveats: Patients chose their chemotherapy backbone, so the trial is randomised for the antibody but not for the chemotherapy.; KRAS exon 2 wild-type only; extended RAS and sidedness were analysed afterwards.; Enrolment spanned seven years during which supportive care and later-line options changed.

## Sources

- JAMA 2017: https://doi.org/10.1001/jama.2017.7105
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28632865/
- Europe PMC full text (PMC5545896): https://europepmc.org/article/MED/28632865

## Connected records

- key papers: [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/), [Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials](https://onco.cc/key-papers/paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- fronts: [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- technologies: [Anti-angiogenic therapy](https://onco.cc/technologies/antiangiogenic/), [Monoclonal antibodies](https://onco.cc/technologies/monoclonal-antibody/)
- targets: [EGFR](https://onco.cc/targets/egfr/), [KRAS](https://onco.cc/targets/kras/), [VEGF / VEGFR](https://onco.cc/targets/vegf/)
- drugs: [Bevacizumab](https://onco.cc/drugs/bevacizumab/), [Cetuximab](https://onco.cc/drugs/cetuximab/), [FOLFIRI (5-FU, leucovorin, irinotecan)](https://onco.cc/drugs/folfiri/), [FOLFOX (5-FU, leucovorin, oxaliplatin)](https://onco.cc/drugs/folfox/)
- companies: [Alliance for Clinical Trials in Oncology](https://onco.cc/companies/alliance-oncology/), [SWOG Cancer Research Network](https://onco.cc/companies/swog/)
- terms: [Sidedness (left vs right colon)](https://onco.cc/terms/sidedness/)
- people: [Alan P. Venook](https://onco.cc/people/alan-venook/), [Heinz-Josef Lenz](https://onco.cc/people/heinz-josef-lenz/)
- bottlenecks: [Failures are hidden](https://onco.cc/bottlenecks/b-negative-results/)
- journals: [JAMA](https://onco.cc/journals/jama/)
- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/)

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