ERBB2 Exon 20 Mutation-Guided Trastuzumab Deruxtecan Therapy in Metastatic Lung Adenocarcinoma with Low HER2 Expression: A Case Report.
5 affiliations
- 1Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People's Republic of China.
- 2Jiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People's Republic of China.
- 3Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People's Republic of China.
- 4The School of Public Administration, Southwestern University of Finance and Economics, Chengdu, 611130, People's Republic of China.
- 5Department of Vascular Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People's Republic of China.
Abstract
HER2 mutations are uncommon in lung adenocarcinoma, and treatment options become limited after failure of standard systemic therapies. We report a 69-year-old woman with metastatic lung adenocarcinoma involving multiple lymph nodes, bone, and the left adrenal gland. Histopathological and immunohistochemical examinations strongly supported a diagnosis of primary pulmonary adenocarcinoma. Targeted next-generation sequencing (NGS) performed at initial diagnosis in January 2024 identified an ERBB2 exon 20 in-frame insertion mutation (p.Y772_A775dup). The patient received six sequential treatment regimens, including platinum-based chemotherapy, PD-1 inhibitor therapy, antiangiogenic therapy, and palliative radiotherapy. Initial tumor regression was observed, but sustained disease control was not achieved. Following further disease progression, the previously identified ERBB2 mutation was reassessed by the multidisciplinary team in 2025. HER2 immunohistochemistry showed an IHC score of 1+. Based on the activating ERBB2 mutation, trastuzumab deruxtecan (T-DXd) was initiated in June 2025 at a fixed dose of 200 mg per administration (approximately 3.2 mg/kg), lower than the standard starting dose for HER2-mutant NSCLC. Five doses were administered between June and November 2025. Serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels decreased markedly after treatment. Serial chest computed tomography indicated radiological disease stabilization for approximately 5 months, with no clinically significant treatment-related adverse events documented. This case highlights the value of molecular profiling in identifying actionable ERBB2 mutations despite low HER2 protein expression. It also provides a real-world observation of disease stabilization with a lower-than-standard initial dose of T-DXd, although conclusions regarding reduced-dose efficacy cannot be drawn from a single case.
Related
- Dramatic response to trastuzumab-deruxtecan in metastatic HER2-overexpressing vulvar extramammary Paget's disease: A case report
- Progression-free survival of 23 months with second-line trastuzumab deruxtecan in HER2-positive gastroesophageal junction adenocarcinoma: a case report
- First-line durvalumab in combination with trastuzumab deruxtecan in women with locally advanced unresectable or metastatic, hormone-receptor-negative, HER2-low breast cancer: multicenter, open-label, phase 1b/2 BEGONIA platform trial
- Managing trastuzumab deruxtecan-related adverse events in patients with metastatic breast cancer: insights from a worldwide survey of the Hermione EDUcational project
- Case Report: Trastuzumab-deruxtecan as 11th line therapy in a metastasized ovarian clear cell carcinoma patient expressing HER2 1+
BibTeX
@article{gao2026erbb2,
title = {{ERBB2 Exon 20 Mutation-Guided Trastuzumab Deruxtecan Therapy in Metastatic Lung Adenocarcinoma with Low HER2 Expression: A Case Report.}},
author = {Zhao-Feng Gao and Xu Wen and Jia-Qi Yu and Jun Zhang and Qian-Yu Chen and Xin-Wei Zhou and Xue-Song He and Peng-Li Wang},
journal = {OncoTargets and therapy},
year = {2026},
month = nov,
doi = {10.2147/ott.s653854},
url = {https://europepmc.org/article/MED/42997584},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - ERBB2 Exon 20 Mutation-Guided Trastuzumab Deruxtecan Therapy in Metastatic Lung Adenocarcinoma with Low HER2 Expression: A Case Report.
AU - Zhao-Feng Gao
AU - Xu Wen
AU - Jia-Qi Yu
AU - Jun Zhang
AU - Qian-Yu Chen
AU - Xin-Wei Zhou
AU - Xue-Song He
AU - Peng-Li Wang
PY - 2026
DA - 2026/11/02
JO - OncoTargets and therapy
DO - 10.2147/ott.s653854
UR - https://europepmc.org/article/MED/42997584
AB - HER2 mutations are uncommon in lung adenocarcinoma, and treatment options become limited after failure of standard systemic therapies. We report a 69-year-old woman with metastatic lung adenocarcinoma involving multiple lymph nodes, bone, and the left adrenal gland. Histopathological and immunohistochemical examinations strongly supported a diagnosis of primary pulmonary adenocarcinoma. Targeted next-generation sequencing (NGS) performed at initial diagnosis in January 2024 identified an ERBB2 exon 20 in-frame insertion mutation (p.Y772_A775dup). The patient received six sequential treatment regimens, including platinum-based chemotherapy, PD-1 inhibitor therapy, antiangiogenic therapy, and palliative radiotherapy. Initial tumor regression was observed, but sustained disease control was not achieved. Following further disease progression, the previously identified ERBB2 mutation was reassessed by the multidisciplinary team in 2025. HER2 immunohistochemistry showed an IHC score of 1+. Based on the activating ERBB2 mutation, trastuzumab deruxtecan (T-DXd) was initiated in June 2025 at a fixed dose of 200 mg per administration (approximately 3.2 mg/kg), lower than the standard starting dose for HER2-mutant NSCLC. Five doses were administered between June and November 2025. Serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels decreased markedly after treatment. Serial chest computed tomography indicated radiological disease stabilization for approximately 5 months, with no clinically significant treatment-related adverse events documented. This case highlights the value of molecular profiling in identifying actionable ERBB2 mutations despite low HER2 protein expression. It also provides a real-world observation of disease stabilization with a lower-than-standard initial dose of T-DXd, although conclusions regarding reduced-dose efficacy cannot be drawn from a single case.
SN - 1178-6930
ER -