Efficacy and safety of antibody drug conjugate therapy in patients with human epidermal growth factor receptor 2‑positive non‑small cell lung cancer: A single‑arm systematic review and meta‑analysis

Zhao,Fanfei; Niu,Tantan; Zheng,Yang; Huo,Gengwei; Huang,Chun

doi:10.3892/ol.2025.15227

Efficacy and safety of antibody drug conjugate therapy in patients with human epidermal growth factor receptor 2‑positive non‑small cell lung cancer: A single‑arm systematic review and meta‑analysis

Authors:
- Fanfei Zhao
- Tantan Niu
- Yang Zheng
- Gengwei Huo
- Chun Huang
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Affiliations: Department of Thoracic Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, P.R. China
Published online on: August 13, 2025 https://doi.org/10.3892/ol.2025.15227
Article Number: 481
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Antibody drug conjugates (ADCs) have demonstrated high levels of efficacy in treating non‑small cell lung cancer (NSCLC). Thus, the present study aimed to explore the efficacy and adverse effects of different types of ADCs targeting human epidermal growth factor receptor 2 (HER‑2). PubMed, Web of Science, Embase and Cochrane Library were exhaustively searched for articles and conference abstracts describing ADC clinical trials that focused on HER‑2. Notably, all articles were published before December 30, 2024. The present study aimed to investigate objective response rate (ORR), disease control rate (DCR), median progression‑free survival (PFS) and adverse event (AE) incidence in targeted NSCLC. The results of the present study revealed that the ORR for HER‑2 NSCLC was 41.8%. Furthermore, the ORR was 26.0, 38.1 and 57.3% for the Ado‑trastuzumab emtansine (T‑DM1), trastuzumab rezetecan (SHR‑A1811) and trastuzumab deruxtecan (T‑DXd) subgroups, respectively. Results of the present study revealed that the DCR of HER‑2‑positive NSCLC following treatment with ADC was 91.6%. Moreover, the PFS time following treatment with ADC was 2.6, 9.5 and 10.5 months in the T‑DM1, SHR‑A1811 and T‑DXd subgroups, respectively. These results were more optimal than those obtained using alternative agents, such as HER‑2‑tyrosine kinase inhibitor (TKI)‑targeted therapy, humanized monoclonal antibodies and trastuzumab‑based therapy, with ORRs of 22.0, 23.0 and 26.0%, DCRs of 59.0, 39.0 and 63.0%, and PFS times of 5.5, 3.1 and 4.6 months, respectively. The results of the present study also indicated that the total incidence of AEs was 96.1%, and the incidence of AEs at grade 3 or higher was 42.4%. Notably, the incidence of AEs in the TDM‑1, SHR‑A1811 and T‑DXd subgroups was 20.0, 47.0 and 47.2%, respectively. In conclusion, the present study revealed that the efficacy of ADCs was superior to that of HER‑2‑TKI‑targeted therapies, humanized monoclonal antibodies and trastuzumab‑based therapies. AEs were manageable, with a low incidence of AEs at grade 3 or higher. Notably, T‑DXd demonstrated the highest level of antitumor activity. In conclusion, the results of the present study may assist clinicians in selecting the optimal therapeutic option for the treatment of NSCLC.

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