{"entity":{"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","aka":[],"tldr":"Pooling 2,159 patients from six trials showed that which side of the colon a tumour started on decides whether an EGFR antibody helps at all: a clear survival gain on the left, none on the right.","summary":"Arnold, Lueza, Douillard and colleagues retrospectively investigated the influence of primary tumour location in patients with unresectable RAS wild-type metastatic colorectal cancer in six randomised trials (CRYSTAL, FIRE-3, CALGB 80405, PRIME, PEAK and 20050181), comparing chemotherapy plus an EGFR antibody with chemotherapy or chemotherapy plus bevacizumab. Hazard ratios for overall and progression-free survival and odds ratios for response were pooled across studies, and the predictive value was evaluated by pooling the study-level interaction between treatment effect and tumour side.\n\nPrimary tumour location and RAS status were available for 2,159 of the 5,760 randomised patients (37.5 percent): 515 right-sided and 1,644 left-sided.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2017","url":"https://doi.org/10.1093/annonc/mdx175"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28407110/"},{"label":"Europe PMC full text (PMC6246616)","url":"https://europepmc.org/article/MED/28407110"}],"tags":["colorectal-evidence"],"related":["paper-heinemann-fire-3-cetuximab-vs-bevacizumab-lancet-oncol-2014","paper-venook-calgb-80405-cetuximab-vs-bevacizumab-jama-2017","paper-douillard-prime-panitumumab-ras-nejm-2013","paper-esmo-metastatic-colorectal-cancer-guideline-ann-oncol-2023","ras-wild-type"],"cancers":["colorectal"],"sections":["targeted-therapy"],"technologies":["monoclonal-antibody"],"targets":["egfr","kras","vegf","nras"],"drugs":["cetuximab","panitumumab","bevacizumab"],"companies":[],"institutions":[],"pathways":["ras-mapk"],"terms":["sidedness","cms-subtypes","wild-type"],"trials":["paradigm","crystal-fire3"],"people":["eric-van-cutsem","josep-tabernero","andres-cervantes","heinz-josef-lenz","volker-heinemann","alan-venook"],"bottlenecks":["b-biomarker-validation"],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2017,"doi":"10.1093/annonc/mdx175","pmid":"28407110","authors":"Arnold D, Lueza B, Douillard JY, et al.","paperType":"meta-analysis","findings":["Right-sided tumours had a worse prognosis in both control and experimental arms: overall survival hazard ratios 2.03 (95 percent CI 1.69 to 2.42) and 1.38 (1.17 to 1.63).","EGFR antibody benefit in left-sided tumours: overall survival hazard ratio 0.75 (0.67 to 0.84) and progression-free survival 0.78 (0.70 to 0.87).","No benefit in right-sided tumours: 1.12 (0.87 to 1.45) and 1.12 (0.87 to 1.44); p for interaction <0.001 and 0.002.","Response odds ratios 2.12 (1.77 to 2.55) on the left against 1.47 (0.94 to 2.29) on the right (p for interaction 0.07)."],"whatItMeans":"The analysis that put 'left-sided, RAS and BRAF wild-type' into every guideline as the anti-EGFR population, and made an anatomical fact into a treatment-selection biomarker.","caveats":["Retrospective pooling on 37.5 percent of the randomised patients, which the authors themselves say demands caution.","Side is a proxy for biology (BRAF, mismatch repair deficiency, consensus molecular subtype) that is now measurable directly.","None of the six trials tested a whole treatment sequence, so the analysis speaks only to the first-line choice."],"changedPractice":true,"participants":2159},"route":"/key-papers/paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017/","neighbours":{"paper":[{"id":"paper-venook-calgb-80405-cetuximab-vs-bevacizumab-jama-2017","kind":"paper","name":"Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in KRAS wild-type advanced or metastatic colorectal cancer (CALGB/SWOG 80405)","route":"/key-papers/paper-venook-calgb-80405-cetuximab-vs-bevacizumab-jama-2017/"},{"id":"paper-heinemann-fire-3-cetuximab-vs-bevacizumab-lancet-oncol-2014","kind":"paper","name":"FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3)","route":"/key-papers/paper-heinemann-fire-3-cetuximab-vs-bevacizumab-lancet-oncol-2014/"},{"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-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/"}],"biomarker":[{"id":"ras-wild-type","kind":"biomarker","name":"RAS wild-type (extended KRAS and NRAS testing)","route":"/biomarkers/ras-wild-type/"}],"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":"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/"},{"id":"vegf","kind":"target","name":"VEGF / VEGFR","route":"/targets/vegf/"}],"drug":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},{"id":"panitumumab","kind":"drug","name":"Panitumumab","route":"/drugs/panitumumab/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"term":[{"id":"cms-subtypes","kind":"term","name":"Consensus molecular subtypes (CMS1-4)","route":"/terms/cms-subtypes/"},{"id":"sidedness","kind":"term","name":"Sidedness (left vs right colon)","route":"/terms/sidedness/"},{"id":"wild-type","kind":"term","name":"Wild-type (WT)","route":"/terms/wild-type/"}],"trial":[{"id":"crystal-fire3","kind":"trial","name":"CRYSTAL & FIRE-3","route":"/trials/crystal-fire3/"},{"id":"paradigm","kind":"trial","name":"PARADIGM","route":"/trials/paradigm/"}],"person":[{"id":"alan-venook","kind":"person","name":"Alan P. Venook","route":"/people/alan-venook/"},{"id":"andres-cervantes","kind":"person","name":"Andrés Cervantes","route":"/people/andres-cervantes/"},{"id":"eric-van-cutsem","kind":"person","name":"Eric Van Cutsem","route":"/people/eric-van-cutsem/"},{"id":"heinz-josef-lenz","kind":"person","name":"Heinz-Josef Lenz","route":"/people/heinz-josef-lenz/"},{"id":"josep-tabernero","kind":"person","name":"Josep Tabernero","route":"/people/josep-tabernero/"},{"id":"volker-heinemann","kind":"person","name":"Volker Heinemann","route":"/people/volker-heinemann/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"}],"journal":[{"id":"annals-of-oncology","kind":"journal","name":"Annals of Oncology","route":"/journals/annals-of-oncology/"}],"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/"}]}}