{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T11:59:35Z","timestamp":1776167975122,"version":"3.50.1"},"reference-count":19,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Epidermal growth factor receptor (EGFR)-kinase domain duplication (KDD) represents an atypical mutation distinct from classical EGFR mutations in lung adenocarcinoma (LUAD). Although first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs) have demonstrated clinical activity in EGFR-KDD, the mechanisms of acquired resistance in this setting remain poorly characterized. Herein, we present a LUAD patient with EGFR-KDD who achieved a sustained initial response to afatinib lasting 67 months before developing acquired resistance. Re-biopsy with next-generation sequencing (NGS) uncovered EGFR T790M, accompanied by EGFR amplification and EGFR M766T. The patient was switched to firmonertinib, with subsequent tumor regression. We reviewed published EGFR-KDD cases that had both acquired resistance to first- or second-generation EGFR-TKIs and corresponding repeat biopsy findings. Five of the eleven cases harbored EGFR T790M, yielding a prevalence of 45%, which is similar to that seen in classical EGFR mutations. This case suggests that EGFR T790M mediates acquired resistance to first- and second-generation EGFR-TKIs in EGFR-KDD, mirroring the resistance pattern observed in classical EGFR mutations.<\/jats:p>","DOI":"10.3390\/curroncol33040214","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T10:29:08Z","timestamp":1776162548000},"page":"214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Acquired Resistance to Afatinib Mediated by EGFR T790M in Lung Adenocarcinoma Patients Harboring EGFR-KDD: A Case Report and Literature Review"],"prefix":"10.3390","volume":"33","author":[{"given":"Qian","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanchao","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pingli","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"ref_1","first-page":"10","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. 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