Zhao Fanfei, Niu Tantan, Zheng Yang, Huo Gengwei, Huang Chun
Department of Thoracic Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, P.R. China.
Department of Thoracic Oncology, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China.
Oncol Lett. 2025 Aug 13;30(4):481. doi: 10.3892/ol.2025.15227. eCollection 2025 Oct.
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.
抗体药物偶联物（ADCs）已在治疗非小细胞肺癌（NSCLC）中显示出高效性。因此，本研究旨在探讨不同类型靶向人表皮生长因子受体2（HER-2）的ADCs的疗效和不良反应。通过全面检索PubMed、Web of Science、Embase和Cochrane图书馆，查找描述聚焦于HER-2的ADC临床试验的文章和会议摘要。值得注意的是，所有文章均在2024年12月30日前发表。本研究旨在调查靶向NSCLC的客观缓解率（ORR）、疾病控制率（DCR）、中位无进展生存期（PFS）和不良事件（AE）发生率。本研究结果显示，HER-2 NSCLC的ORR为41.8%。此外，ado曲妥珠单抗（T-DM1）、曲妥珠单抗瑞泽卡（SHR-A1811）和曲妥珠单抗德卢替康（T-DXd）亚组的ORR分别为26.0%、38.1%和57.3%。本研究结果显示，用ADC治疗后HER-2阳性NSCLC的DCR为91.6%。此外，T-DM1、SHR-A1811和T-DXd亚组用ADC治疗后的PFS时间分别为2.6个月、9.5个月和10.5个月。这些结果比使用其他药物（如HER-2酪氨酸激酶抑制剂（TKI）靶向治疗、人源化单克隆抗体和基于曲妥珠单抗的治疗）所获得的结果更优，其ORR分别为22.0%、23.0%和26.0%，DCR分别为59.0%、39.0%和63.0%，PFS时间分别为5.5个月、3.1个月和4.6个月。本研究结果还表明，AE的总发生率为96.1%，3级及以上AE的发生率为42.4%。值得注意的是，TDM-1、SHR-A1811和T-DXd亚组的AE发生率分别为20.0%、47.0 和47.2%。总之，本研究表明，ADCs的疗效优于HER-2-TKI靶向治疗、人源化单克隆抗体和基于曲妥珠单抗的治疗。AE是可控的，3级及以上AE的发生率较低。值得注意的是，T-DXd显示出最高水平的抗肿瘤活性。总之，本研究结果可能有助于临床医生为NSCLC的治疗选择最佳治疗方案。
