{"entity":{"id":"paper-lenz-cms-calgb-swog-80405-jco-2019","kind":"paper","name":"Impact of consensus molecular subtype on survival in patients with metastatic colorectal cancer: results from CALGB/SWOG 80405","aka":[],"tldr":"In the one randomised trial where the four gene-activity subtypes were measured, they predicted not only how long people lived but which biological drug worked better: the immune subtype did better with bevacizumab and the canonical subtype with cetuximab.","summary":"The consensus molecular subtypes were characterised with a NanoString gene expression panel on primary tumours from 581 patients enrolled in CALGB/SWOG 80405, a phase 3 trial comparing the addition of bevacizumab or cetuximab to infusional fluorouracil, leucovorin and oxaliplatin or irinotecan as first-line treatment of advanced colorectal cancer. The subtypes were highly prognostic for overall survival (p less than 0.001) and progression-free survival (p less than 0.001), and predictive for both (interaction p less than 0.001 for overall survival and 0.0032 for progression-free survival). In the CMS1 cohort, patients treated with bevacizumab lived significantly longer than those treated with cetuximab (p less than 0.001); in the CMS2 cohort, patients treated with cetuximab lived significantly longer than those treated with bevacizumab (p = 0.0046).","asOf":"2026-09-24","links":[{"label":"Lenz et al., J Clin Oncol 2019: consensus molecular subtype and survival in 581 CALGB/SWOG 80405 patients","url":"https://doi.org/10.1200/JCO.18.02258"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31042420/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["rna-seq"],"targets":["egfr","vegf"],"drugs":["bevacizumab","cetuximab"],"companies":[],"institutions":[],"pathways":[],"terms":["cms-subtypes"],"trials":[],"people":["heinz-josef-lenz","alan-venook"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.18.02258","pmid":"31042420","authors":"Lenz HJ, Ou FS, Venook AP, et al.","paperType":"rct","findings":["Consensus molecular subtypes prognostic for overall and progression-free survival (p less than 0.001).","CMS1: longer overall survival with bevacizumab than cetuximab (p less than 0.001).","CMS2: longer overall survival with cetuximab than bevacizumab (p = 0.0046)."],"whatItMeans":"It is the strongest evidence that the consensus subtypes could choose between the two first-line biologicals, and the clearest statement of why they have not: it is a retrospective analysis of a subset of one trial, on an assay nobody has validated for clinical use.","caveats":["Retrospective on 581 of the trial's patients, so subgroup effects may be chance.","Primary tumour tissue and bulk RNA, with the stromal confound described by Isella and Calon.","No prospective subtype-directed trial has been run."],"changedPractice":false,"participants":581},"route":"/key-papers/paper-lenz-cms-calgb-swog-80405-jco-2019/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"technology":[{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"}],"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":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}],"term":[{"id":"cms-subtypes","kind":"term","name":"Consensus molecular subtypes (CMS1-4)","route":"/terms/cms-subtypes/"}],"person":[{"id":"alan-venook","kind":"person","name":"Alan P. Venook","route":"/people/alan-venook/"},{"id":"heinz-josef-lenz","kind":"person","name":"Heinz-Josef Lenz","route":"/people/heinz-josef-lenz/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}]}}