{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:19:16Z","timestamp":1787239156105,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T00:00:00Z","timestamp":1761436800000},"content-version":"vor","delay-in-days":25,"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":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Uncommon EGFR mutations, including G719X, L861Q, S768I, and compound mutations, present therapeutic challenges due to limited prospective evidence and variable drug sensitivity. Although later\u2010generation (i.e., second\u2010 and third\u2010) EGFR\u2010TKIs have shown benefit in some subtypes, real\u2010world data is limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed patients with advanced or recurrent NSCLC harboring uncommon EGFR mutations diagnosed between 2014 and 2019 at Keio University Hospital and affiliated hospitals. Clinical data were updated through May 2023. EGFR mutations were detected using commercial assays. Common mutations and exon 20 insertions were excluded unless coexisting as compound mutations. Survival outcomes were estimated using the Kaplan\u2013Meier method and compared by log\u2010rank test; hazard ratios were calculated using the Cox proportional hazards model. Swimmer plots depicted treatment duration by subtype and EGFR\u2010TKI agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 35 patients, G719X was the most frequently detected mutation, followed by L861Q and S768I. In addition to these single mutations, various compound mutations involving combinations of G719X, L861Q, S768I, and other rare variants were also observed. While first\u2010generation EGFR\u2010TKIs were frequently used initially, 71% of patients eventually received a later\u2010generation EGFR\u2010TKI. These patients had significantly longer OS (47.7 vs. 15.5\u2009months;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0177). Multivariate analysis identified non\u2010use of later\u2010generation EGFR\u2010TKIs, liver metastases, and poor performance status as independent poor prognostic factors. Afatinib showed favorable treatment duration in G719X and compound mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Later\u2010generation EGFR\u2010TKIs were associated with improved outcomes in patients with uncommon EGFR mutations, with afatinib showing favorable treatment duration in G719X and compound subtypes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1759-7714.70179","type":"journal-article","created":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T22:44:26Z","timestamp":1761518666000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical Outcomes of Later\u2010Generation\n                    <scp>EGFR<\/scp>\n                    \u2010\n                    <scp>TKIs<\/scp>\n                    for Uncommon\n                    <scp>EGFR<\/scp>\n                    Mutations in\n                    <scp>NSCLC<\/scp>\n                    : A Multicenter Real\u2010World Study"],"prefix":"10.1111","volume":"16","author":[{"given":"Lisa","family":"Shigematsu","sequence":"first","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5719-2697","authenticated-orcid":false,"given":"Tetsuo","family":"Tani","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinnosuke","family":"Ikemura","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine Keio University School of Medicine  Tokyo Japan"},{"name":"Department of Respiratory Medicine Graduate 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