{"entity":{"id":"paper-douillard-prime-extended-ras-panitumumab-nejm-2013","kind":"paper","name":"Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer","aka":[],"tldr":"Testing only the two commonest spots in KRAS was not enough: another one in six patients called wild-type turned out to carry a RAS mutation somewhere else, and they did no better on the antibody than the ones already excluded.","summary":"In a prospective-retrospective analysis of the PRIME trial, the efficacy and safety of panitumumab plus FOLFOX4 against FOLFOX4 alone were assessed by RAS (KRAS or NRAS) and BRAF mutation status. A total of 639 patients whose tumours lacked KRAS exon 2 mutations had results for at least one of KRAS exon 3 or 4, NRAS exon 2, 3 or 4, or BRAF exon 15, with 90% overall ascertainment. Among 512 patients with no RAS mutation, progression-free survival was 10.1 months with panitumumab-FOLFOX4 against 7.9 with FOLFOX4 alone (hazard ratio 0.72) and overall survival 26.0 against 20.2 months (hazard ratio 0.78). A total of 108 patients (17%) with non-mutated KRAS exon 2 had other RAS mutations, and those mutations were associated with inferior progression-free and overall survival on panitumumab-FOLFOX4, consistent with the findings in KRAS exon 2 mutants. BRAF mutations were a negative prognostic factor.","asOf":"2026-09-24","links":[{"label":"Douillard et al., N Engl J Med 2013: PRIME, extended RAS testing and panitumumab-FOLFOX4","url":"https://doi.org/10.1056/NEJMoa1305275"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24024839/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":["kras","nras","egfr","braf"],"drugs":["panitumumab"],"companies":[],"institutions":[],"pathways":["ras-mapk"],"terms":["wild-type","ngs"],"trials":[],"people":["salvatore-siena"],"bottlenecks":[],"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":["108 of 639 KRAS exon 2 wild-type patients (17%) carried another RAS mutation.","RAS wild-type: overall survival 26.0 against 20.2 months (hazard ratio 0.78).","Other RAS mutations predicted lack of benefit, exactly as KRAS exon 2 mutations do."],"whatItMeans":"It moved the label and every guideline from KRAS exon 2 testing to extended RAS testing of KRAS and NRAS exons 2, 3 and 4, which is the threshold in use today.","caveats":["Prospective-retrospective; 10% of patients had no extended RAS result.","BRAF was prognostic rather than clearly predictive in this analysis.","Sidedness was analysed later."],"changedPractice":true,"participants":1183},"route":"/key-papers/paper-douillard-prime-extended-ras-panitumumab-nejm-2013/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"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":"panitumumab","kind":"drug","name":"Panitumumab","route":"/drugs/panitumumab/"},{"id":"therascreen-cdx","kind":"drug","name":"therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF)","route":"/drugs/therascreen-cdx/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"term":[{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"},{"id":"wild-type","kind":"term","name":"Wild-type (WT)","route":"/terms/wild-type/"}],"person":[{"id":"salvatore-siena","kind":"person","name":"Salvatore Siena","route":"/people/salvatore-siena/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"trial":[{"id":"paradigm","kind":"trial","name":"PARADIGM","route":"/trials/paradigm/"}],"biomarker":[{"id":"kras-g12d","kind":"biomarker","name":"KRAS G12D (and other non-G12C KRAS mutations)","route":"/biomarkers/kras-g12d/"}]}}