注射用重组人源化抗HER2单克隆抗体-美登素偶联物（RC48-ADC）在不同HER2表达水平乳腺癌患者中的真实世界应用：疗效与安全性分析
Real-world application of disitamab vedotin (RC48-ADC) in patients with breast cancer with different HER2 expression levels: efficacy and safety analysis.
作者信息
Wang Ke, Xu Ting, Wu Jing, Yuan Yuan, Guan Xiaoxiang, Zhu Chengjun
机构信息
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210009, People's Republic of China.
Department of Chemotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, People's Republic of China.
出版信息
Oncologist. 2024 Nov 16. doi: 10.1093/oncolo/oyae304.
BACKGROUND
Disitamab vedotin (RC48-ADC), an antibody-drug conjugate (ADC), combines specific antibody disitamab with cytotoxicity monomethyl auristatin E to effectively target the human epidermal growth factor receptor 2 (HER2) protein on tumor cells for precise elimination. Recent studies have demonstrated that RC48-ADC offers therapeutic benefits for patients with HER2-positive and HER2-low-expression breast cancer (BC). However, a thorough exploration of its efficacy and safety in real-world settings for patients with metastatic breast cancer (mBC) is currently lacking.
METHODS
This retrospective, multicenter, real-world study included patients with mBC who received RC48-ADC from September 2021 to March 2024. These patients include HER2-positive BC and HER2-low-expression BC. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), restricted mean survival time, objective response rate (ORR), and disease control rate (DCR). Factors affecting efficacy and the occurrence of treatment-related adverse events (TRAE) were evaluated.
RESULTS
The study included a cohort of 89 patients with mBC, with 48 of those being identified as HER2-positive. As of March 2024, 22 deaths were recorded, with an immature median OS. Total PFS varied from 1.0 to 31.2 months, with a median of 5.5 months (95% CI, 4.368-6.632). HER2-positive patients exhibited prolonged PFS compared with HER2-low-expression patients (6.6 months vs 4.1 months, P = .023). The overall ORR stood at 25.8% (95% CI, 0.178-0.358), with higher rates observed in HER2-positive patients compared with HER2-low-expression patients (31.3% vs 19.5%). Similarly, the overall DCR was 78.7% (95% CI, 0.691-0.859), with HER2-positive patients demonstrating superior DCR compared with HER2-low-expression patients (83.3% vs 73.2%). Notably, HER2 expression emerged as the primary determinant of RC48-ADC efficacy. The most prevalent TRAE among all patients included leukopenia (21.3%) and alopecia (20.2%).
CONCLUSION
RC48-ADC showcases promising efficacy and manageable safety in patients with both HER2-positive and HER2-low-expression mBC.
背景
迪西他单抗维泊妥珠单抗（RC48-ADC）是一种抗体药物偶联物（ADC），它将特异性抗体迪西他单抗与细胞毒性药物单甲基奥瑞他汀E结合，可有效靶向肿瘤细胞上的人表皮生长因子受体2（HER2）蛋白，实现精准清除。近期研究表明，RC48-ADC对HER2阳性和HER2低表达乳腺癌（BC）患者具有治疗益处。然而，目前尚缺乏对其在转移性乳腺癌（mBC）患者真实世界中的疗效和安全性的全面探索。
方法
这项回顾性、多中心、真实世界研究纳入了2021年9月至2024年3月接受RC48-ADC治疗的mBC患者。这些患者包括HER2阳性BC和HER2低表达BC。主要终点为无进展生存期（PFS）。次要终点包括总生存期（OS）、受限平均生存时间、客观缓解率（ORR）和疾病控制率（DCR）。评估了影响疗效和治疗相关不良事件（TRAE）发生的因素。
结果
该研究纳入了89例mBC患者队列，其中48例被确定为HER2阳性。截至2024年3月，记录到22例死亡，中位OS尚未成熟。总PFS为1.0至31.2个月，中位值为5.5个月（95%CI，4.368 - 6.632）。与HER2低表达患者相比，HER2阳性患者的PFS更长（6.6个月对4.1个月，P = 0.023）。总体ORR为25.8%（95%CI，0.178 - 0.358），HER2阳性患者的ORR高于HER2低表达患者（31.3%对19.5%）。同样，总体DCR为78.7%（95%CI，0.691 - 0.859），HER2阳性患者的DCR优于HER2低表达患者（83.3%对73.2%）。值得注意的是，HER2表达是RC48-ADC疗效的主要决定因素。所有患者中最常见的TRAE包括白细胞减少（21.3%）和脱发（20.2%）。
结论
RC48-ADC在HER2阳性和HER2低表达mBC患者中展现出了有前景的疗效和可管理的安全性。
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