{"entity":{"id":"paradigm","kind":"trial","name":"PARADIGM","aka":[],"tldr":"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.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02394795","url":"https://clinicaltrials.gov/study/NCT02394795"},{"label":"ASCO 2022 plenary","url":"https://ascopubs.org/doi/10.1200/JCO.2022.40.17_suppl.LBA1"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["monoclonal-antibody"],"targets":["egfr","vegf"],"drugs":["panitumumab","bevacizumab","folfox"],"companies":["takeda"],"institutions":[],"pathways":[],"terms":["sidedness"],"trials":["prime","calgb-80405","opus","cairo5"],"people":["yoshino-takayuki"],"bottlenecks":[],"keyPapers":["paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017","paper-douillard-prime-panitumumab-ras-nejm-2013","paper-paradigm-jama-2023"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02394795","phase":"3","setting":"First-line RAS wild-type metastatic colorectal cancer: panitumumab + mFOLFOX6 vs bevacizumab + mFOLFOX6","sponsor":"Takeda (Japan)","result":"OS 37.9 vs 34.3 months (HR 0.82) in left-sided RAS wild-type disease.","started":"2015-05-29","startedType":"actual","yearReported":2022,"enrolled":823,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival, left-sided","primary":true,"unit":"months","arms":[{"name":"Panitumumab + mFOLFOX6","value":37.9},{"name":"Bevacizumab + mFOLFOX6","value":34.3}],"hr":0.82,"ci":[0.68,0.99],"p":"0.031","source":"https://ascopubs.org/doi/10.1200/JCO.2022.40.17_suppl.LBA1"}],"replication":"Replicates FIRE-3 (cetuximab vs bevacizumab with FOLFIRI, OS benefit) and the CALGB/SWOG 80405 sidedness analysis."},"route":"/trials/paradigm/","neighbours":{"cancer":[{"id":"colon-cancer","kind":"cancer","name":"Colon cancer (adenocarcinoma of the colon)","route":"/cancers/colon-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"technology":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"vegf","kind":"target","name":"VEGF / VEGFR","route":"/targets/vegf/"}],"drug":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"folfox","kind":"drug","name":"FOLFOX (5-FU, leucovorin, oxaliplatin)","route":"/drugs/folfox/"},{"id":"panitumumab","kind":"drug","name":"Panitumumab","route":"/drugs/panitumumab/"}],"company":[{"id":"takeda","kind":"company","name":"Takeda","route":"/companies/takeda/"}],"term":[{"id":"sidedness","kind":"term","name":"Sidedness (left vs right colon)","route":"/terms/sidedness/"}],"trial":[{"id":"cairo5","kind":"trial","name":"CAIRO5","route":"/trials/cairo5/"},{"id":"calgb-80405","kind":"trial","name":"CALGB/SWOG 80405","route":"/trials/calgb-80405/"},{"id":"opus","kind":"trial","name":"OPUS","route":"/trials/opus/"},{"id":"prime","kind":"trial","name":"PRIME","route":"/trials/prime/"}],"person":[{"id":"yoshino-takayuki","kind":"person","name":"Takayuki Yoshino","route":"/people/yoshino-takayuki/"}],"paper":[{"id":"paper-esmo-metastatic-colorectal-cancer-guideline-ann-oncol-2023","kind":"paper","name":"Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","route":"/key-papers/paper-esmo-metastatic-colorectal-cancer-guideline-ann-oncol-2023/"},{"id":"paper-paradigm-jama-2023","kind":"paper","name":"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","route":"/key-papers/paper-paradigm-jama-2023/"},{"id":"paper-douillard-prime-panitumumab-ras-nejm-2013","kind":"paper","name":"Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME)","route":"/key-papers/paper-douillard-prime-panitumumab-ras-nejm-2013/"},{"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/"}],"pairing":[{"id":"anti-egfr-left-sided","kind":"pairing","name":"Anti-EGFR antibody + chemotherapy in left-sided RAS/BRAF wild-type mCRC","route":"/pairings/anti-egfr-left-sided/"}],"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/"}],"biomarker":[{"id":"ras-wild-type","kind":"biomarker","name":"RAS wild-type (extended KRAS and NRAS testing)","route":"/biomarkers/ras-wild-type/"}]}}