CASE REPORT article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1631768
Trastuzumab deruxtecan for the treatment of metastatic non-small cell lung cancer harboring HER2 non-exon 19/20 mutations: A case series
Provisionally accepted
- 1Hainan Cancer Hospital, Hainan, China
- 2The School of Clinical Medicine, Fujian Medical University, Fuzhou, China
- 3Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- 4Guangzhou University of Chinese Medicine, Guangzhou, China
- 5Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, Guangzhou, China
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Background: Patients with human epidermal growth factor receptor 2 (HER2)-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 HER2-mutant metastatic NSCLC, but the evidence in those with HER2 non-exon 19/20 mutations is scarce.Methods: We reported treatment information and outcomes of four patients with metastatic NSCLC harboring HER2 non-exon 19/20 mutations who were treated with T-DXd. Results: All the four patients had metastatic lung adenocarcinoma and reached partial response to T-DXd treatment. A 57-year-old female patient with HER2 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 HER2 exon 3 T126A mutation had disease progression after 16-month treatment. The other two patients (one with HER2 exon 21 H878Y mutation and one with HER2 exon 17 V659E mutation) were continuing T-DXd treatment, both with a PFS of more than 6 months. No interstitial lung disease or grade ≥3 adverse events occurred in these four patients.Conclusion: The potential of T-DXd in patients with metastatic NSCLC harboring HER2 non-exon 19/20 mutations is considerable, which deserves to be validated in large-sample studies.
Keywords: trastuzumab deruxtecan, Non-small cell lung cancer, Human epidermal growth factor receptor 2, Mutation, case series
Received: 20 May 2025; Accepted: 25 Jul 2025.
Copyright: © 2025 Meng, Du, Liu, Huang, Chen and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yanping Du, The School of Clinical Medicine, Fujian Medical University, Fuzhou, China
Chunxia He, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, Guangzhou, China
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