{"entity":{"id":"prime","kind":"trial","name":"PRIME","aka":["Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy"],"tldr":"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.","status":"positive","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov NCT00364013","url":"https://clinicaltrials.gov/study/NCT00364013"},{"label":"PRIME: panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (New England Journal of Medicine 2013)","url":"https://doi.org/10.1056/NEJMoa1305275"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["monoclonal-antibody","cytotoxic-chemotherapy"],"targets":["egfr","kras","nras","braf"],"drugs":["panitumumab","folfox","oxaliplatin","fluorouracil"],"companies":["amgen"],"institutions":[],"pathways":[],"terms":["sidedness"],"trials":["crystal-fire3","paradigm","opus"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00364013","phase":"3","setting":"Previously untreated metastatic colorectal cancer: FOLFOX4 with or without panitumumab, analysed by extended RAS status","sponsor":"Amgen","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.","yearReported":2013,"enrolled":1183,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival (RAS wild-type)","primary":true,"unit":"months","arms":[{"name":"FOLFOX4 plus panitumumab","value":26},{"name":"FOLFOX4","value":20.2}],"hr":0.78,"ci":[0.62,0.99],"p":"0.04","source":"https://doi.org/10.1056/NEJMoa1305275"},{"endpoint":"Progression-free survival (RAS wild-type)","unit":"months","arms":[{"name":"FOLFOX4 plus panitumumab","value":10.1},{"name":"FOLFOX4","value":7.9}],"hr":0.72,"ci":[0.58,0.9],"p":"0.004","source":"https://doi.org/10.1056/NEJMoa1305275"}],"replication":"The same extended-RAS effect was found retrospectively in CRYSTAL, OPUS and FIRE-3 and prospectively in PARADIGM."},"route":"/trials/prime/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"},{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"nras","kind":"target","name":"NRAS","route":"/targets/nras/"}],"drug":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"},{"id":"folfox","kind":"drug","name":"FOLFOX (5-FU, leucovorin, oxaliplatin)","route":"/drugs/folfox/"},{"id":"oxaliplatin","kind":"drug","name":"Oxaliplatin","route":"/drugs/oxaliplatin/"},{"id":"panitumumab","kind":"drug","name":"Panitumumab","route":"/drugs/panitumumab/"}],"company":[{"id":"amgen","kind":"company","name":"Amgen","route":"/companies/amgen/"}],"term":[{"id":"sidedness","kind":"term","name":"Sidedness (left vs right colon)","route":"/terms/sidedness/"}],"trial":[{"id":"crystal-fire3","kind":"trial","name":"CRYSTAL & FIRE-3","route":"/trials/crystal-fire3/"},{"id":"co-17","kind":"trial","name":"NCIC CO.17","route":"/trials/co-17/"},{"id":"opus","kind":"trial","name":"OPUS","route":"/trials/opus/"},{"id":"paradigm","kind":"trial","name":"PARADIGM","route":"/trials/paradigm/"}],"biomarker":[{"id":"ras-wild-type","kind":"biomarker","name":"RAS wild-type (extended KRAS and NRAS testing)","route":"/biomarkers/ras-wild-type/"}]}}