{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T15:19:39Z","timestamp":1770909579347,"version":"3.50.1"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with <jats:italic>human epidermal growth factor receptor 2<\/jats:italic> (<jats:italic>HER2<\/jats:italic>)-mutant non-small cell lung cancer (NSCLC) have poor prognosis. Trastuzumab deruxtecan (T-DXd) is the first targeted therapy approved for the treatment of patients with <jats:italic>HER2<\/jats:italic>-mutant metastatic NSCLC, but the evidence in those with <jats:italic>HER2<\/jats:italic> non-exon 19\/20 mutations is scarce.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We reported treatment information and outcomes of four patients with metastatic NSCLC harboring <jats:italic>HER2<\/jats:italic> non-exon 19\/20 mutations who were treated with T-DXd.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All the four patients had metastatic lung adenocarcinoma and reached partial response to T-DXd treatment. A 57-year-old female patient with <jats:italic>HER2<\/jats:italic> exon 17 V659E mutation received T-DXd as later-line treatment. Treatment was ongoing and the progression-free survival (PFS) had reached 13 months. Three patients received first-line T-DXd treatment. One patient with <jats:italic>HER2<\/jats:italic> exon 3 T126A mutation had disease progression after 16-month treatment. The other two patients (one with <jats:italic>HER2<\/jats:italic> exon 21 H878Y mutation and one with <jats:italic>HER2<\/jats:italic> exon 17 V659E mutation) were continuing T-DXd treatment, both with a PFS of more than 6 months. No interstitial lung disease or grade \u22653 adverse events occurred in these four patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The potential of T-DXd in patients with metastatic NSCLC harboring <jats:italic>HER2<\/jats:italic> non-exon 19\/20 mutations is considerable, which deserves to be validated in large-sample studies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1631768","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T05:31:50Z","timestamp":1754976710000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Trastuzumab deruxtecan for the treatment of metastatic non-small cell lung cancer harboring HER2 non-exon 19\/20 mutations: four case 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