# PARADIGM

Source: https://onco.cc/trials/paradigm/  
OnCo record `paradigm` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Proved that for RAS-normal tumours starting on the left side of the colon, an EGFR antibody beats the VEGF antibody as first partner for chemotherapy.

## Summary

Left-sided primaries: OS 37.9 vs 34.3 months (HR 0.82), the longest median OS in a first-line phase 3 at the time; no benefit in right-sided tumours. Confirmed the sidedness principle from FIRE-3 and CALGB 80405 subgroup analyses and made 'left-sided, RAS/BRAF wild-type' the anti-EGFR population in guidelines.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT02394795
- Phase: 3
- Setting: First-line RAS wild-type metastatic colorectal cancer: panitumumab + mFOLFOX6 vs bevacizumab + mFOLFOX6
- Sponsor: Takeda (Japan)
- Enrolled: 823
- Result: OS 37.9 vs 34.3 months (HR 0.82) in left-sided RAS wild-type disease.
- Outcomes: Overall survival, left-sided: Panitumumab + mFOLFOX6 37.9 months vs Bevacizumab + mFOLFOX6 34.3 months, HR 0.82
- Replication: Replicates FIRE-3 (cetuximab vs bevacizumab with FOLFIRI, OS benefit) and the CALGB/SWOG 80405 sidedness analysis.

## Sources

- ClinicalTrials.gov NCT02394795: https://clinicaltrials.gov/study/NCT02394795
- ASCO 2022 plenary: https://ascopubs.org/doi/10.1200/JCO.2022.40.17_suppl.LBA1

## Connected records

- cancers: [Colon cancer (adenocarcinoma of the colon)](https://onco.cc/cancers/colon-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- technologies: [Monoclonal antibodies](https://onco.cc/technologies/monoclonal-antibody/)
- targets: [EGFR](https://onco.cc/targets/egfr/), [VEGF / VEGFR](https://onco.cc/targets/vegf/)
- drugs: [Bevacizumab](https://onco.cc/drugs/bevacizumab/), [FOLFOX (5-FU, leucovorin, oxaliplatin)](https://onco.cc/drugs/folfox/), [Panitumumab](https://onco.cc/drugs/panitumumab/)
- companies: [Takeda](https://onco.cc/companies/takeda/)
- terms: [Sidedness (left vs right colon)](https://onco.cc/terms/sidedness/)
- trials: [CAIRO5](https://onco.cc/trials/cairo5/), [CALGB/SWOG 80405](https://onco.cc/trials/calgb-80405/), [OPUS](https://onco.cc/trials/opus/), [PRIME](https://onco.cc/trials/prime/)
- people: [Takayuki Yoshino](https://onco.cc/people/yoshino-takayuki/)
- key papers: [Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up](https://onco.cc/key-papers/paper-esmo-metastatic-colorectal-cancer-guideline-ann-oncol-2023/), [Panitumumab vs Bevacizumab Added to Standard First-line Chemotherapy and Overall Survival Among Patients With RAS Wild-type, Left-Sided Metastatic Colorectal Cancer: A Randomized Clinical Trial](https://onco.cc/key-papers/paper-paradigm-jama-2023/), [Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME)](https://onco.cc/key-papers/paper-douillard-prime-panitumumab-ras-nejm-2013/), [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/)
- pairings: [Anti-EGFR antibody + chemotherapy in left-sided RAS/BRAF wild-type mCRC](https://onco.cc/pairings/anti-egfr-left-sided/)
- 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/)
- biomarkers: [RAS wild-type (extended KRAS and NRAS testing)](https://onco.cc/biomarkers/ras-wild-type/)

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