{"entity":{"id":"paper-douillard-prime-panitumumab-ras-nejm-2013","kind":"paper","name":"Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME)","aka":[],"tldr":"Looking beyond the one KRAS exon everyone tested found that a further 17 percent of patients carried a RAS mutation and were harmed rather than helped by the antibody. Testing widened overnight.","summary":"Douillard, Oliner, Siena and colleagues assessed the efficacy and safety of panitumumab plus FOLFOX4 against FOLFOX4 alone by RAS (KRAS or NRAS) and BRAF mutation status, in a prospective-retrospective analysis of PRIME. Six hundred and thirty-nine patients whose tumours had no KRAS exon 2 mutation had results for at least one of KRAS exon 3 or 4, NRAS exon 2, 3 or 4, or BRAF exon 15; the overall rate of RAS status ascertainment was 90 percent.\n\nNo new safety signals were identified, and BRAF mutation was a negative prognostic factor rather than a predictor of antibody benefit.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2013","url":"https://doi.org/10.1056/NEJMoa1305275"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24024839/"}],"tags":["colorectal-evidence"],"related":["paper-van-cutsem-crystal-cetuximab-folfiri-nejm-2009","paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017"],"cancers":["colorectal"],"sections":["targeted-therapy"],"technologies":["monoclonal-antibody"],"targets":["egfr","kras","braf"],"drugs":["panitumumab","folfox","oxaliplatin"],"companies":["amgen"],"institutions":[],"pathways":["ras-mapk"],"terms":["sidedness"],"trials":[],"people":["salvatore-siena","josep-tabernero"],"bottlenecks":["b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2013,"doi":"10.1056/NEJMoa1305275","pmid":"24024839","authors":"Douillard JY, Oliner KS, Siena S, et al.","paperType":"rct","findings":["Among 512 patients without any RAS mutation, progression-free survival 10.1 against 7.9 months (hazard ratio 0.72, 95 percent CI 0.58 to 0.90, p=0.004).","Overall survival 26.0 against 20.2 months (hazard ratio 0.78, 0.62 to 0.99, p=0.04).","108 of 639 patients (17 percent) with non-mutated KRAS exon 2 had other RAS mutations, and these were associated with inferior outcomes on panitumumab-FOLFOX4.","BRAF mutation was a negative prognostic factor."],"whatItMeans":"Extended RAS testing (KRAS and NRAS exons 2, 3 and 4) became the standard before any EGFR antibody, and about one in six patients who would previously have been treated is now spared a drug that would have made things worse.","caveats":["Prospective-retrospective: the RAS analysis was planned but performed after the trial read out, on 90 percent of samples.","The harm signal in the additional RAS-mutant group rests on 108 patients.","Sidedness was analysed only later, in the pooled analysis of six trials."],"changedPractice":true,"participants":639},"route":"/key-papers/paper-douillard-prime-panitumumab-ras-nejm-2013/","neighbours":{"paper":[{"id":"paper-van-cutsem-crystal-cetuximab-folfiri-nejm-2009","kind":"paper","name":"Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer (CRYSTAL)","route":"/key-papers/paper-van-cutsem-crystal-cetuximab-folfiri-nejm-2009/"},{"id":"paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017","kind":"paper","name":"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","route":"/key-papers/paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017/"},{"id":"paper-fakih-codebreak-300-sotorasib-panitumumab-nejm-2023","kind":"paper","name":"Sotorasib plus panitumumab in refractory colorectal cancer with mutated KRAS G12C (CodeBreaK 300)","route":"/key-papers/paper-fakih-codebreak-300-sotorasib-panitumumab-nejm-2023/"},{"id":"paper-kras-colorectal-j-clin-oncol-2008","kind":"paper","name":"Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer","route":"/key-papers/paper-kras-colorectal-j-clin-oncol-2008/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"section":[{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"technology":[{"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/"}],"drug":[{"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/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"term":[{"id":"sidedness","kind":"term","name":"Sidedness (left vs right colon)","route":"/terms/sidedness/"}],"person":[{"id":"josep-tabernero","kind":"person","name":"Josep Tabernero","route":"/people/josep-tabernero/"},{"id":"salvatore-siena","kind":"person","name":"Salvatore Siena","route":"/people/salvatore-siena/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"roadmap":[{"id":"colorectal-roadmap","kind":"roadmap","name":"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","route":"/roadmaps/colorectal-roadmap/"}]}}