{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:09:51Z","timestamp":1789556991059,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Non\u2013small cell lung cancers (NSCLC) harboring uncommon epidermal growth factor receptor (EGFR) mutations (UMs) are clinically heterogeneous, and the optimal first\u2010line EGFR tyrosine kinase inhibitor (EGFR\u2010TKI), as well as the role of subsequent immune checkpoint inhibitor (ICI)\u2013based regimens, remains uncertain. We conducted a multicenter retrospective cohort study including patients with advanced or recurrent non\u2010squamous NSCLC harboring UMs who received first\u2010line afatinib or osimertinib between January 2015 and January 2024 at 29 hospitals in Japan, excluding exon 20 insertions and de novo T790M mutations. Inverse probability of treatment weighting adjusted baseline imbalances, and post\u2013EGFR\u2010TKI treatment patterns were evaluated. Among 162 patients (afatinib,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200995; osimertinib,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200967), weighted analyses demonstrated no significant differences in time to treatment failure (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.61\u20131.77) or overall survival (HR, 1.34; 95% CI, 0.73\u20132.44). Afatinib was associated with higher response rates and more frequent adverse events requiring dose reduction. Subgroup analyses suggested differential treatment effects according to mutation subtype, with osimertinib favoring L861X mutations and afatinib favoring compound mutations. Among 56 patients who received subsequent systemic therapy, clinical outcomes were comparable between ICI plus platinum doublet and platinum doublet alone. These findings indicate that afatinib and osimertinib provide comparable survival outcomes as first\u2010line therapies for NSCLC with UMs, with treatment effects varying by molecular subtype, while subsequent ICI\u2010based regimens may confer limited additional benefit.\n                  <\/jats:p>","DOI":"10.1111\/cas.70400","type":"journal-article","created":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T12:00:14Z","timestamp":1780228814000},"page":"2236-2246","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Afatinib Versus Osimertinib for Non\u2010Small Cell Lung Cancer With Uncommon\n                    <scp>EGFR<\/scp>\n                    Mutations: Real\u2010World Outcomes"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4016-7335","authenticated-orcid":false,"given":"Yutaro","family":"Nagano","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine and Allergology Sapporo Medical University School of Medicine  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Yokouchi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine NHO Hokkaido Cancer Center  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Yamanashi Prefectural Central Hospital  Yamanashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Honjo","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Sapporo Minami\u2010Sanjo Hospital  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2540-5878","authenticated-orcid":false,"given":"Toshiyuki","family":"Sumi","sequence":"additional","affiliation":[{"name":"Department of Respiratory 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Allergology Sapporo Medical University School of Medicine  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Oizumi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine NHO Hokkaido Cancer Center  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,31]]},"reference":[{"issue":"9","key":"e_1_2_13_2_1","first-page":"2892","article-title":"EGFR Mutation Incidence in Non\u2010Small\u2010Cell Lung Cancer of Adenocarcinoma Histology: A Systematic Review and Global Map by Ethnicity (mutMapII)","volume":"5","author":"Midha A.","year":"2015","journal-title":"American Journal of Cancer 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