{"entity":{"id":"paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017","kind":"paper","name":"Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies","aka":[],"tldr":"Sequencing 860 patients with advanced lung adenocarcinoma as they arrived in clinic answered a question nobody had measured: how many of them actually get a treatment because of the test. Just over a third did.","summary":"Eight hundred and sixty patients with metastatic lung adenocarcinoma were analysed prospectively for mutations in more than 300 cancer-associated genes. Potentially actionable genetic events were stratified into four levels by the published evidence that the alteration confers sensitivity to a standard or investigational therapy. Overall, 319 of 860 patients, 37.1%, received a matched therapy guided by the molecular profile. Excluding alterations already associated with standard-of-care therapy, 69 of 478 patients, 14.4%, received matched therapy, with clinical benefit in 52% of them. Use of matched therapy was strongly influenced by the level of pre-existing evidence that the alteration predicts drug response. Analysis of genes mutated significantly more often in tumours without a known actionable alteration nominated STK11 and KEAP1 as possible targetable mitogenic drivers.","asOf":"2026-09-25","links":[{"label":"Jordan et al., Cancer Discov 2017: prospective molecular characterisation of 860 metastatic lung adenocarcinomas (MSK-IMPACT)","url":"https://doi.org/10.1158/2159-8290.CD-16-1337"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28336552/"},{"label":"cBioPortal study lung_msk_2017 (MSK, Cancer Discov 2017; 915 MSK-IMPACT samples from the 860 prospectively sequenced metastatic lung adenocarcinomas)","url":"https://www.cbioportal.org/study/summary?id=lung_msk_2017"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["cgp"],"targets":["egfr","kras","alk","met","her2","braf","stk11","keap1","ret","ros1"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":["nsclc-signalling","rtk-activation","ras-mapk"],"terms":["driver-mutation","ngs","stk11-keap1"],"trials":[],"people":["gregory-riely"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2017,"doi":"10.1158/2159-8290.CD-16-1337","pmid":"28336552","authors":"Jordan EJ, Kim HR, Arcila ME, et al.","paperType":"observational","findings":["37.1% of prospectively sequenced patients received a therapy matched to the result.","Outside standard-of-care alterations, 14.4% received a matched therapy, with benefit in 52%.","The level of published evidence, not the presence of the alteration, determined whether treatment followed.","STK11 and KEAP1 emerged as the recurrent alterations in tumours with no other actionable driver."],"whatItMeans":"It is the honest accounting of precision oncology in the disease where it works best: broad sequencing changes treatment for about one patient in three, and the bottleneck is evidence rather than detection.","caveats":["A single referral centre with early access to trials, so the matched-therapy rate is a ceiling rather than an average.","Benefit was assessed without a control group.","Panel sequencing, so fusion and copy-number detection depend on the panel's design."],"changedPractice":false,"participants":860},"route":"/key-papers/paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017/","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/"}],"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":"keap1","kind":"target","name":"KEAP1","route":"/targets/keap1/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"met","kind":"target","name":"MET","route":"/targets/met/"},{"id":"ret","kind":"target","name":"RET","route":"/targets/ret/"},{"id":"ros1","kind":"target","name":"ROS1","route":"/targets/ros1/"},{"id":"stk11","kind":"target","name":"STK11","route":"/targets/stk11/"}],"institution":[{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"}],"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":"stk11-keap1","kind":"term","name":"STK11 / KEAP1 co-mutations","route":"/terms/stk11-keap1/"}],"person":[{"id":"gregory-riely","kind":"person","name":"Gregory J. Riely","route":"/people/gregory-riely/"}],"journal":[{"id":"cancer-discovery","kind":"journal","name":"Cancer Discovery","route":"/journals/cancer-discovery/"}]}}