{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T20:02:49Z","timestamp":1787860969365,"version":"build-2784847793"},"reference-count":13,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T00:00:00Z","timestamp":1581984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Osimertinib is the most promising treatment option for patients with epidermal growth factor receptor (<jats:italic>EGFR<\/jats:italic>) mutation\u2010positive non\u2010small cell lung cancer (NSCLC) with acquired T790M resistance. However, recent studies have suggested that osimertinib could increase the frequency of serious adverse events (AEs) if administered immediately after immune checkpoint inhibitor (ICI) treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this single\u2010institution retrospective study conducted from May 2016 to January 2019, osimertinib was administered to 47 patients with pretreated advanced NSCLC harboring the <jats:italic>EGFR<\/jats:italic> mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 47 patients, 20 (42.6%) were men and 27 (57.4%) were women. The median age was 71\u2009years (range 37\u201383\u2009years). A total of 19 patients (40.4%) had a smoking history. Furthermore, seven patients (14.9%) received osimertinib immediately after nivolumab therapy, while 40 patients (85.1%) were treated with osimertinib after treatment with drugs other than nivolumab. The frequency of grade 3 or 4 hepatotoxicity was significantly higher in patients with nivolumab prior to osimertinib (4\/7; 57.1%) than in those treated with drugs other than nivolumab prior to osimertinib (2\/40; 5.0%) (<jats:italic>P<\/jats:italic> = 0.0026). Liver biopsies were performed in two patients who received osimertinib immediately after nivolumab. In both patients, CD\u20108\u2010positive T cell infiltration was predominantly observed in the liver tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The use of osimertinib immediately after nivolumab significantly increased the frequency of grade 3 or higher hepatotoxicity in patients with advanced NSCLC harboring <jats:italic>EGFR<\/jats:italic> mutation acquired T790M resistance.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1759-7714.13363","type":"journal-article","created":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T13:12:10Z","timestamp":1582031530000},"page":"1045-1051","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Severe hepatotoxicity due to osimertinib after nivolumab therapy in patients with non\u2010small cell lung cancer harboring <i>EGFR<\/i> mutation"],"prefix":"10.1111","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7194-6459","authenticated-orcid":false,"given":"Ou","family":"Yamaguchi","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Comprehensive Cancer Center Saitama Medical University International Medical Center  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5548-7686","authenticated-orcid":false,"given":"Kyoichi","family":"Kaira","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Comprehensive Cancer Center Saitama Medical University International Medical Center  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonori","family":"Kawasaki","sequence":"additional","affiliation":[{"name":"Department of Pathology Saitama Medical University International Medical Center  Saitama 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