{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:24:35Z","timestamp":1788441875888,"version":"build-2803163510"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T00:00:00Z","timestamp":1660003200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T00:00:00Z","timestamp":1660003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Onc"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Osimertinib, a mutant-specific third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is emerging as the preferred first-line of treatment for EGFR-mutant lung cancer. However, osimertinib resistance inevitably develops among patients treated with the drug. The modal resistance mechanisms of osimertinib include the occurrence of epithelial transition factor (c-MET) amplification and C797S mutation, whereas rare mutations are presented as case reports. Recently, the L718Q\/V mutation in exon 18 of EGFR has been reported to contribute to one of the possible mechanisms of resistance. The clinical features and subsequent treatment strategies for this mutation require further research. This study retrospectively enrolled NSCLC patients with the L718Q\/V mutation from 2017 to 2021 at the Cancer Hospital of the University of the Chinese Academy of Sciences (Zhejiang Cancer Hospital), as well as additional patients with the same mutation from PubMed literature, to summarize the clinical features of the mutation. The association between the detection of L718Q\/V and resistance to osimertinib, as well as impacts on the therapeutic process and outcome, was analyzed. We included a total of two patients diagnosed at Zhejiang Cancer Hospital and twelve patients from the literature. Of the fourteen total patients, 64.3% were male and 35.7% were female. The average age of the group was 60.2\u00a0years (range 45\u201372). A history of tobacco use was common among the group. In all of the cases we considered, the L718Q\/V mutation was secondary to the L858R mutation. The second-generation TKI afatinib was found to provide a high disease control rate (DCR) (85.7%, 6\/7) and relatively low objective response rate (ORR) (42\/9%, 3\/7). The median progression free survival (mPFS) for this treatment reached 2\u00a0months (1\u20136\u00a0months). The patients failed to benefit from chemotherapy combined with immunotherapy or other TKI medications. Due to the limited number of cases considered in this study, future studies should explore drugs that more precisely target the L718Q\/V mutation of EGFR exon 18.<\/jats:p>","DOI":"10.1007\/s12672-022-00537-7","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T10:02:52Z","timestamp":1660039372000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["L718Q\/V mutation in exon 18 of EGFR mediates resistance to osimertinib: clinical features and treatment"],"prefix":"10.1007","volume":"13","author":[{"given":"Meihui","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fajun","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0404-5153","authenticated-orcid":false,"given":"Hongyang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,9]]},"reference":[{"issue":"7","key":"537_CR1","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1056\/NEJMoa1612674","volume":"376","author":"TS Mok","year":"2017","unstructured":"Mok TS, Wu Y-L, Ahn M-J, et al. Osimertinib or Platinum-Pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017;376(7):629\u201340.","journal-title":"N Engl J Med"},{"issue":"11","key":"537_CR2","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1016\/j.annonc.2020.08.2100","volume":"31","author":"VA Papadimitrakopoulou","year":"2020","unstructured":"Papadimitrakopoulou VA, Mok TS, Han JY, et al. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann Oncol. 2020;31(11):1536\u201344.","journal-title":"Ann Oncol"},{"issue":"2","key":"537_CR3","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1056\/NEJMoa1713137","volume":"378","author":"JC Soria","year":"2018","unstructured":"Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113\u201325.","journal-title":"N Engl J Med"},{"issue":"1","key":"537_CR4","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1056\/NEJMoa1913662","volume":"382","author":"SS Ramalingam","year":"2020","unstructured":"Ramalingam SS, Vansteenkiste J, Planchard D, et al. Overall survival with Osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020;382(1):41\u201350.","journal-title":"N Engl J Med"},{"issue":"24","key":"537_CR5","doi-asserted-by":"publisher","first-page":"6195","DOI":"10.1158\/1078-0432.CCR-18-1542","volume":"24","author":"X Le","year":"2018","unstructured":"Le X, Puri S, Negrao MV, et al. Landscape of EGFR-dependent and -independent resistance mechanisms to osimertinib and continuation therapy beyond progression in EGFR-mutant NSCLC. 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Front Oncol. 2021;11: 649843.","journal-title":"Front Oncol"},{"issue":"1","key":"537_CR22","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1186\/s12885-019-5915-7","volume":"19","author":"J Liu","year":"2019","unstructured":"Liu J, Jin B, Su H, Qu X, Liu Y. Afatinib helped overcome subsequent resistance to osimertinib in a patient with NSCLC having leptomeningeal metastasis baring acquired EGFR L718Q mutation: a case report. BMC Cancer. 2019;19(1):702.","journal-title":"BMC Cancer"},{"issue":"12","key":"537_CR23","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.jtho.2019.07.018","volume":"14","author":"W Fang","year":"2019","unstructured":"Fang W, Gan J, Huang Y, Zhou H, Zhang L. Acquired EGFR L718V mutation and loss of T790M-mediated resistance to osimertinib in a patient with NSCLC who responded to afatinib. J Thorac Oncol. 2019;14(12):274\u20135.","journal-title":"J Thorac Oncol"},{"issue":"6","key":"537_CR24","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/j.cllc.2021.03.018","volume":"22","author":"LE Raez","year":"2021","unstructured":"Raez LE, Carracedo C, Drusbosky LM, Velez M, Carlisle J, Stinchcombe T. EGFR L718V (+)\/T790M (-) as a mechanism of resistance in patients with metastatic non-small-cell lung cancer with EGFR L858R Mutations. Clin Lung Cancer. 2021;22(6):817\u20139.","journal-title":"Clin Lung Cancer"}],"container-title":["Discover Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-022-00537-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12672-022-00537-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-022-00537-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T12:32:34Z","timestamp":1660307554000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12672-022-00537-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,9]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["537"],"URL":"https:\/\/doi.org\/10.1007\/s12672-022-00537-7","relation":{},"ISSN":["2730-6011"],"issn-type":[{"value":"2730-6011","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,9]]},"assertion":[{"value":"21 June 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 August 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 August 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The protocol was approved by Medical Ethics Committee of Zhejiang Cancer Hospital. The patients\/participants provided their written informed consent to participate in this study. As the patient specimens were collected in a retrospective approach, and the patients were deceased, exempt written informed consents were also approved by the Medical Ethics Committee of Zhejiang Cancer.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"72"}}