{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:03:21Z","timestamp":1778216601387,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T00:00:00Z","timestamp":1650240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972164"],"award-info":[{"award-number":["81972164"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>MET<\/jats:italic> dysregulation has been implicated in the development of primary and secondary resistance to EGFR tyrosine kinase inhibitor (TKI) therapy. However, the clinicopathological characteristics and outcomes of patients harboring <jats:italic>EGFR<\/jats:italic>\u2010sensitive mutations and de novo <jats:italic>MET<\/jats:italic> amplifications still need to be explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 54 patients from our hospital with non\u2010small cell lung cancer harboring <jats:italic>EGFR<\/jats:italic>\u2010sensitive mutations and\/or de novo <jats:italic>MET<\/jats:italic> amplifications were included in this study. Survival rates were estimated by the Kaplan\u2013Meier method with log\u2010rank statistics. Lung cancer organoids (LCOs) were generated from patient\u2010derived malignant pleural effusion to perform drug sensitivity assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifty\u2010four patients with the appropriate clinicopathological characteristics were enrolled. <jats:italic>MET<\/jats:italic> FISH was performed in 40 patients who were stratified accordingly into two groups: <jats:italic>EGFR<\/jats:italic>+\/<jats:italic>MET<\/jats:italic>amp\u2010 (<jats:italic>n<\/jats:italic>\u00a0=\u00a022) and <jats:italic>EGFR<\/jats:italic>+\/<jats:italic>MET<\/jats:italic>amp\u2009+\u2009(<jats:italic>n<\/jats:italic>\u00a0=\u00a018). Survival rates for <jats:italic>EGFR<\/jats:italic>+\/<jats:italic>MET<\/jats:italic>amp\u2010 and <jats:italic>EGFR<\/jats:italic>+\/<jats:italic>MET<\/jats:italic>amp\u2009+\u2009patients respectively, were as follows: the median progression\u2010free survival (PFS) was 12.1 and 1.9\u00a0months (<jats:italic>p<\/jats:italic>&lt;0.001); the median post\u2010progression overall survival (pOS) was 25.6 and 11.6\u00a0months (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.023); the median overall survival (OS) was 33.2 and 12.7\u00a0months (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.013). Drug testing conducted in LCOs derived from malignant pleural effusion from <jats:italic>EGFR<\/jats:italic>+\/<jats:italic>MET<\/jats:italic>amp\u2009+\u2009patients showed that dual targeted therapy was more effective than TKI monotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>EGFR<\/jats:italic>+\/<jats:italic>MET<\/jats:italic>amp\u2009+\u2009patients treated with first\u2010line TKI monotherapy had poor clinical outcomes. Dual targeted therapy showed potent anticancer activity in the LCO drug testing assay, suggesting that it is a promising first\u2010line treatment for <jats:italic>EGFR<\/jats:italic>+\/<jats:italic>MET<\/jats:italic>amp\u2009+\u2009patients. Randomized controlled trials are needed to further validate these results.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1759-7714.14429","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T04:08:28Z","timestamp":1650341308000},"page":"1619-1630","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Clinical outcomes of <i><scp>EGFR<\/scp><\/i>+\/<scp><i>MET<\/i>amp<\/scp>+\u2009vs. <scp><i>EGFR<\/i><\/scp>+\/<scp><i>MET<\/i>amp<\/scp>\u2010 untreated patients with advanced non\u2010small cell lung cancer"],"prefix":"10.1111","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8094-9720","authenticated-orcid":false,"given":"Kai\u2010Cheng","family":"Peng","sequence":"first","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou China"},{"name":"Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun\u2010Wei","family":"Su","sequence":"additional","affiliation":[{"name":"Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Xie","sequence":"additional","affiliation":[{"name":"Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han\u2010Min","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei\u2010Mei","family":"Fang","sequence":"additional","affiliation":[{"name":"Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen\u2010Feng","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu\u2010Qing","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou China"},{"name":"Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu\u2010Hui","family":"Guan","sequence":"additional","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou China"},{"name":"Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Su","sequence":"additional","affiliation":[{"name":"Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital 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