Real-world application of disitamab vedotin (RC48-ADC) in patients with breast cancer with different HER2 expression levels: efficacy and safety analysis.

IF 4.8 2区医学 Q1 ONCOLOGY

Oncologist Pub Date : 2024-11-16 DOI:10.1093/oncolo/oyae304

Ke Wang, Ting Xu, Jing Wu, Yuan Yuan, Xiaoxiang Guan, Chengjun Zhu

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引用次数: 0

Abstract

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.

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迪西他单抗维多汀（RC48-ADC）在不同 HER2 表达水平的乳腺癌患者中的实际应用：疗效与安全性分析。

背景：地西他单抗维多汀（RC48-ADC）是一种抗体-药物共轭物（ADC），它将特异性抗体地西他单抗与细胞毒性单甲基金刚烷E结合在一起，能有效靶向肿瘤细胞上的人表皮生长因子受体2（HER2）蛋白，从而精确清除肿瘤细胞。最近的研究表明，RC48-ADC 对 HER2 阳性和 HER2 低表达乳腺癌（BC）患者有治疗效果。然而，目前还缺乏在真实世界中对转移性乳腺癌（mBC）患者的疗效和安全性的深入探讨：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 月期间接受 RC48-ADC 治疗的 mBC 患者。这些患者包括 HER2 阳性 BC 和 HER2 低表达 BC。主要终点是无进展生存期（PFS）。次要终点包括总生存期（OS）、限制性平均生存时间、客观反应率（ORR）和疾病控制率（DCR）。研究还评估了影响疗效的因素以及治疗相关不良事件（TRAE）的发生情况：该研究共纳入89例mBC患者，其中48例被确定为HER2阳性。截至2024年3月，共有22人死亡，中位OS不成熟。总生存期从1.0个月到31.2个月不等，中位数为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 vs 4.1个月，P = .023）。总体 ORR 为 25.8%（95% CI，0.178-0.358），与 HER2 低表达患者相比，HER2 阳性患者的 ORR 更高（31.3% vs 19.5%）。同样，总体 DCR 为 78.7%（95% CI，0.691-0.859），与 HER2 低表达患者相比，HER2 阳性患者的 DCR 更高（83.3% vs 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对HER2阳性和HER2低表达的mBC患者具有良好的疗效和可控的安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oncologist 医学-肿瘤学

CiteScore

10.40

自引率

3.40%

发文量

309

审稿时长

3-8 weeks

期刊介绍： The Oncologist® is dedicated to translating the latest research developments into the best multidimensional care for cancer patients. Thus, The Oncologist is committed to helping physicians excel in this ever-expanding environment through the publication of timely reviews, original studies, and commentaries on important developments. We believe that the practice of oncology requires both an understanding of a range of disciplines encompassing basic science related to cancer, translational research, and clinical practice, but also the socioeconomic and psychosocial factors that determine access to care and quality of life and function following cancer treatment.