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

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.