# PRIME

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

## TL;DR

The trial that widened the RAS test from two spots in one gene to all of KRAS and NRAS, because patients with any RAS mutation were harmed by the antibody.

## Summary

PRIME randomised 1,183 patients with previously untreated metastatic colorectal cancer to FOLFOX4 with or without panitumumab. The prospective-retrospective RAS analysis tested KRAS exons 3 and 4 and NRAS exons 2, 3 and 4 in patients without KRAS exon 2 mutations, with 90 percent ascertainment. Among 512 patients without any RAS mutation, progression-free survival was 10.1 against 7.9 months (hazard ratio 0.72, 95% CI 0.58 to 0.90, p=0.004) and overall survival 26.0 against 20.2 months (hazard ratio 0.78, 0.62 to 0.99, p=0.04). A further 108 patients, 17 percent of those with wild-type KRAS exon 2, carried other RAS mutations, and in them panitumumab shortened progression-free and overall survival. BRAF mutation was prognostic, not predictive. PRIME is why extended RAS testing, not KRAS exon 2 alone, is mandatory before any EGFR antibody.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-24
- Also known as: Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy
- Registry id: NCT00364013
- Phase: 3
- Setting: Previously untreated metastatic colorectal cancer: FOLFOX4 with or without panitumumab, analysed by extended RAS status
- Sponsor: Amgen
- Enrolled: 1183
- Result: In RAS wild-type disease, overall survival 26.0 against 20.2 months (hazard ratio 0.78); patients with non-exon-2 RAS mutations did worse with panitumumab.
- Outcomes: Overall survival (RAS wild-type): FOLFOX4 plus panitumumab 26 months vs FOLFOX4 20.2 months, HR 0.78; Progression-free survival (RAS wild-type): FOLFOX4 plus panitumumab 10.1 months vs FOLFOX4 7.9 months, HR 0.72
- Replication: The same extended-RAS effect was found retrospectively in CRYSTAL, OPUS and FIRE-3 and prospectively in PARADIGM.

## Sources

- ClinicalTrials.gov NCT00364013: https://clinicaltrials.gov/study/NCT00364013
- PRIME: panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (New England Journal of Medicine 2013): https://doi.org/10.1056/NEJMoa1305275

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Monoclonal antibodies](https://onco.cc/technologies/monoclonal-antibody/)
- targets: [BRAF](https://onco.cc/targets/braf/), [EGFR](https://onco.cc/targets/egfr/), [KRAS](https://onco.cc/targets/kras/), [NRAS](https://onco.cc/targets/nras/)
- drugs: [Cetuximab](https://onco.cc/drugs/cetuximab/), [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [FOLFOX (5-FU, leucovorin, oxaliplatin)](https://onco.cc/drugs/folfox/), [Oxaliplatin](https://onco.cc/drugs/oxaliplatin/), [Panitumumab](https://onco.cc/drugs/panitumumab/)
- companies: [Amgen](https://onco.cc/companies/amgen/)
- terms: [Sidedness (left vs right colon)](https://onco.cc/terms/sidedness/)
- trials: [CRYSTAL & FIRE-3](https://onco.cc/trials/crystal-fire3/), [NCIC CO.17](https://onco.cc/trials/co-17/), [OPUS](https://onco.cc/trials/opus/), [PARADIGM](https://onco.cc/trials/paradigm/)
- biomarkers: [RAS wild-type (extended KRAS and NRAS testing)](https://onco.cc/biomarkers/ras-wild-type/)

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