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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
  • View Affiliations / Copyright

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

Figure 1

Flow chart depicting the literature
screening and selection process.

Figure 2

Forest plot of objective response rate
among patients treated with human epidermal growth factor receptor
2-targeted antibody drug conjugate. ES, effect size (objective
response rate); CI, confidence interval.

Figure 3

Forest plot of objective response rate
subgroup analysis based on drug types. X-axis label: ORR. Events,
number of patients achieving objective response; ORR, objective
response rate; ES, effect size (ORR); CI, confidence interval;
T-DM1, Ado-trastuzumab emtansine; SHR-A1811, trastuzumab rezetecan;
T-DXd, trastuzumab deruxtecan.

Figure 4

Forest plot of disease control rate
among patients treated with human epidermal growth factor receptor
2-targeted antibody drug conjugate. ES, effect size (disease
control rate); CI, confidence interval.

Figure 5

Forest plot of disease control rate
sensitivity analysis. ES, effect size (disease control rate); CI,
confidence interval.

Figure 6

Forest plot of progression-free
survival among patients treated with human epidermal growth factor
receptor 2-targeted antibody drug conjugate. ES, effect size
(progression-free survival); CI, confidence interval.

Figure 7

Forest plot of progression-free
survival subgroup analysis based on drug types. ES, effect size
(progression-free survival); CI, confidence interval.

Figure 8

Forest plot of adverse event incidence
among patients treated with human epidermal growth factor receptor
2-targeted antibody drug conjugate. ES, effect size (AE incidence);
CI, confidence interval.

Figure 9

Forest plot of incidence of adverse
events at grade 3 or higher among patients treated with human
epidermal growth factor receptor 2-targeted antibody drug
conjugate. ES, incidence of adverse events at grade 3 or higher;
CI, confidence interval.

Figure 10

Forest plot of incidence of adverse
events at grade 3 or higher by subgroup based on drug types. ES,
incidence of adverse events at grade 3 or higher; CI, confidence
interval.
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Copy and paste a formatted citation
Spandidos Publications style
Zhao F, Niu T, Zheng Y, Huo G and Huang C: 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. Oncol Lett 30: 481, 2025.
APA
Zhao, F., Niu, T., Zheng, Y., Huo, G., & Huang, C. (2025). 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. Oncology Letters, 30, 481. https://doi.org/10.3892/ol.2025.15227
MLA
Zhao, F., Niu, T., Zheng, Y., Huo, G., Huang, C."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". Oncology Letters 30.4 (2025): 481.
Chicago
Zhao, F., Niu, T., Zheng, Y., Huo, G., Huang, C."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". Oncology Letters 30, no. 4 (2025): 481. https://doi.org/10.3892/ol.2025.15227
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao F, Niu T, Zheng Y, Huo G and Huang C: 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. Oncol Lett 30: 481, 2025.
APA
Zhao, F., Niu, T., Zheng, Y., Huo, G., & Huang, C. (2025). 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. Oncology Letters, 30, 481. https://doi.org/10.3892/ol.2025.15227
MLA
Zhao, F., Niu, T., Zheng, Y., Huo, G., Huang, C."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". Oncology Letters 30.4 (2025): 481.
Chicago
Zhao, F., Niu, T., Zheng, Y., Huo, G., Huang, C."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". Oncology Letters 30, no. 4 (2025): 481. https://doi.org/10.3892/ol.2025.15227
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