{"entity":{"id":"paper-kris-lung-cancer-mutation-consortium-jama-2014","kind":"paper","name":"Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs","aka":[],"tldr":"Fourteen American centres tested a thousand lung adenocarcinomas for ten genes at once and found a driver in about two thirds. The patients whose treatment was chosen to match their driver lived about a year longer.","summary":"From 2009 to 2012, 14 sites enrolled patients with metastatic lung adenocarcinoma and tested their tumours for ten oncogenic drivers. Tumours from 1,007 patients were tested for at least one gene and 733 for all ten. An oncogenic driver was found in 466 of 733, 64%. Among those 733 tumours, 182 had KRAS (25%), 122 sensitising EGFR (17%), 57 ALK rearrangement (8%), 29 other EGFR (4%), 24 two or more genes (3%), 19 ERBB2 (3%), 16 BRAF (2%), 6 PIK3CA, 5 MET amplification, 5 NRAS and 1 MEK1, with no AKT1. Results were used to select a targeted therapy or trial in 275 of 1,007 patients, 28%. Median survival was 3.5 years for the 260 patients with an oncogenic driver who received genotype-directed therapy against 2.4 years for the 318 with a driver who did not, with a propensity-adjusted hazard ratio of 0.69.","asOf":"2026-09-25","links":[{"label":"Kris et al., JAMA 2014: multiplexed driver testing in 1,007 lung adenocarcinomas (Lung Cancer Mutation Consortium)","url":"https://doi.org/10.1001/jama.2014.3741"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24846037/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["cgp","cytogenetics-fish"],"targets":["kras","egfr","alk","her2","braf","pik3ca","met","nras"],"drugs":[],"companies":[],"institutions":["mskcc","vanderbilt-ingram","md-anderson"],"pathways":["nsclc-signalling","rtk-activation","ras-mapk"],"terms":["driver-mutation","ngs","wild-type"],"trials":[],"people":["lecia-sequist"],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2014,"doi":"10.1001/jama.2014.3741","pmid":"24846037","authors":"Kris MG, Johnson BE, Berry LD, et al.","paperType":"observational","findings":["An oncogenic driver in 466 of 733 fully genotyped lung adenocarcinomas, 64%.","KRAS 25%, sensitising EGFR 17%, ALK rearrangement 8%, ERBB2 3%, BRAF 2%.","Multiplexed testing guided treatment in 28% of all patients tested.","Median survival 3.5 against 2.4 years with matched therapy, adjusted hazard ratio 0.69."],"whatItMeans":"It is the study that made multiplex testing standard practice in lung adenocarcinoma, by showing both that most tumours have a driver and that finding it changes what patients receive.","caveats":["Not randomised: patients who received matched therapy differed from those who did not in ways propensity adjustment cannot fully remove.","Ten genes only, so ROS1, RET, NTRK and MET exon 14 were not counted.","Conducted before immunotherapy, so the comparator has changed."],"changedPractice":true,"participants":1007},"route":"/key-papers/paper-kris-lung-cancer-mutation-consortium-jama-2014/","neighbours":{"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"cytogenetics-fish","kind":"technology","name":"Cytogenetics and FISH","route":"/technologies/cytogenetics-fish/"}],"target":[{"id":"alk","kind":"target","name":"ALK","route":"/targets/alk/"},{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"},{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"met","kind":"target","name":"MET","route":"/targets/met/"},{"id":"nras","kind":"target","name":"NRAS","route":"/targets/nras/"},{"id":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/"}],"institution":[{"id":"md-anderson","kind":"institution","name":"MD Anderson Cancer Center","route":"/institutions/md-anderson/"},{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"},{"id":"vanderbilt-ingram","kind":"institution","name":"Vanderbilt-Ingram Cancer Center","route":"/institutions/vanderbilt-ingram/"}],"pathway":[{"id":"nsclc-signalling","kind":"pathway","name":"Non-small cell lung cancer (KEGG map)","route":"/pathways/nsclc-signalling/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"},{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}],"term":[{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"},{"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":"lecia-sequist","kind":"person","name":"Lecia V. Sequist","route":"/people/lecia-sequist/"}],"journal":[{"id":"jama","kind":"journal","name":"JAMA","route":"/journals/jama/"}],"biomarker":[{"id":"alk-fusion","kind":"biomarker","name":"ALK fusion (ALK-positive)","route":"/biomarkers/alk-fusion/"},{"id":"braf-v600e","kind":"biomarker","name":"BRAF V600E (and V600K)","route":"/biomarkers/braf-v600e/"},{"id":"her2-mutation","kind":"biomarker","name":"HER2 (ERBB2) activating mutation","route":"/biomarkers/her2-mutation/"},{"id":"kras-g12c","kind":"biomarker","name":"KRAS G12C","route":"/biomarkers/kras-g12c/"}]}}