# Duration of adjuvant chemotherapy for stage III colon cancer (the IDEA collaboration)

Source: https://onco.cc/key-papers/paper-idea-duration-adjuvant-stage-iii-colon-nejm-2018/  
OnCo record `paper-idea-duration-adjuvant-stage-iii-colon-nejm-2018` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Six trials pooled 12,834 patients to ask whether three months of chemotherapy is as good as six. For lower-risk tumours treated with CAPOX it is, and the nerve damage is far less.

## Summary

Grothey, Sobrero, Shields and colleagues performed a prospective, preplanned, pooled analysis of six randomised phase 3 trials conducted concurrently to evaluate the non-inferiority of three months of FOLFOX or CAPOX against six months in stage III colon cancer. The primary end point was three-year disease-free survival, and non-inferiority could be claimed if the upper limit of the two-sided 95 percent confidence interval of the hazard ratio did not exceed 1.12.

Non-inferiority was not confirmed overall, but the regimen-specific and risk-group results changed practice anyway: three months of CAPOX became standard for T1 to T3 N1 disease and six months of FOLFOX remained standard for T4 or N2 disease.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: colorectal-evidence
- Journal: New England Journal of Medicine
- Year: 2018
- DOI: 10.1056/NEJMoa1713709
- Authors: Grothey A, Sobrero AF, Shields AF, et al.
- Findings: 3,263 recurrence or death events among 12,834 patients; non-inferiority of three months not confirmed overall (hazard ratio 1.07, 95 percent CI 1.00 to 1.15).; Non-inferiority was seen for CAPOX (0.95, 0.85 to 1.06) but not for FOLFOX (1.16, 1.06 to 1.26).; In T1 to T3 N1 disease, three months was non-inferior: three-year disease-free survival 83.1 against 83.3 percent (1.01, 0.90 to 1.12).; In T4 or N2 disease, six months was superior: 64.4 against 62.7 percent (1.12, 1.03 to 1.23, p=0.01).
- What it means: The largest de-escalation exercise in adjuvant oncology, and the reason a patient with a T3 N1 colon cancer is now offered four cycles of CAPOX rather than twelve of FOLFOX, with a fraction of the neuropathy.
- Caveats: The formal non-inferiority question was answered no; practice follows the subgroup and regimen analyses, which were pre-specified but exploratory in combination.; Patients were not randomised between FOLFOX and CAPOX, so the regimen comparison is not randomised evidence.; Quality of life and neuropathy data are reported in the individual trials rather than in the pooled analysis.

## Sources

- N Engl J Med 2018: https://doi.org/10.1056/NEJMoa1713709
- PubMed: https://pubmed.ncbi.nlm.nih.gov/29590544/
- Europe PMC full text (PMC6426127): https://europepmc.org/article/MED/29590544

## Connected records

- key papers: [Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up](https://onco.cc/key-papers/paper-esmo-localised-colon-cancer-guideline-ann-oncol-2020/), [Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer (MOSAIC)](https://onco.cc/key-papers/paper-mosaic-oxaliplatin-adjuvant-colon-nejm-2004/), [Structured exercise after adjuvant chemotherapy for colon cancer (CHALLENGE)](https://onco.cc/key-papers/paper-courneya-challenge-structured-exercise-colon-nejm-2025/)
- cancers: [Colon cancer (adenocarcinoma of the colon)](https://onco.cc/cancers/colon-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- fronts: [Chemotherapy](https://onco.cc/fronts/chemotherapy/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/)
- drugs: [Capecitabine](https://onco.cc/drugs/capecitabine/), [CAPOX (capecitabine, oxaliplatin)](https://onco.cc/drugs/capox/), [FOLFOX (5-FU, leucovorin, oxaliplatin)](https://onco.cc/drugs/folfox/), [Oxaliplatin](https://onco.cc/drugs/oxaliplatin/)
- terms: [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/)
- people: [Takayuki Yoshino](https://onco.cc/people/yoshino-takayuki/), [Thierry André](https://onco.cc/people/thierry-andre/)
- bottlenecks: [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/), [Wrong doses](https://onco.cc/bottlenecks/b-dose-optimisation/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- 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/)
- ideas: [Take ctDNA-guided de-escalation beyond stage II, and stop escalating on a positive result until a trial says it helps](https://onco.cc/ideas/idea-crc-ctdna-de-escalation-beyond-stage-ii/)

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