文章：

抗HER2疗法对HER2阳性转移性乳腺癌患者总生存期的影响：聚焦新兴治疗方案的颅内疗效

Impact of Anti-HER2 Therapies on Overall Survival in Patients with HER2-Positive Metastatic Breast Cancer: Focusing on Intracranial Efficacy of Emerging Treatments

原文发布日期：31 October 2025

DOI: 10.3390/cancers17213520

类型: Article

开放获取: 是

英文摘要：

Therapies targeting human epidermal growth factor receptor 2 (HER2) have substantially improved overall survival in patients with HER2-positive metastatic breast cancer. Approximately 31% of these patients develop brain metastases, representing a significant therapeutic challenge. This review classifies anti-HER2 therapies into three categories: monoclonal antibodies (MABs), antibody-drug conjugates (ADCs), and tyrosine kinase inhibitors (TKIs). The mechanisms of action and clinical impacts of these agents are examined, with particular attention to intracranial efficacy. The introduction of trastuzumab increased overall survival (OS) from 20.3 to 25.1 months compared to chemotherapy alone. The addition of pertuzumab further extended survival to 57.1 months, as demonstrated in the CLEOPATRA trial. Among ADCs, T-DM1 improved OS to 29.9 months versus 25.9 months in the EMILIA trial, while T-DXd extended OS to 52.6 months in DESTINY-Breast03. T-DXd also demonstrated notable intracranial activity, achieving a 64.9% objective response rate in patients with active brain metastases. In the HER2CLIMB trial, tucatinib reduced intracranial progression by 68% and improved OS (24.7 vs. 19.2 months) in patients with active brain metastases. Recent advances have increased median OS from approximately 20 months prior to trastuzumab to over 50 months with current therapies. Future research should focus on optimizing treatment sequencing, refining biomarker-driven approaches, and developing targeted strategies for brain metastases to further improve long-term survival outcomes.

摘要翻译： 

靶向人表皮生长因子受体2（HER2）的治疗显著改善了HER2阳性转移性乳腺癌患者的总生存期。约31%的患者会发生脑转移，这构成了重大的治疗挑战。本综述将抗HER2治疗分为三类：单克隆抗体（MABs）、抗体偶联药物（ADCs）和酪氨酸激酶抑制剂（TKIs）。文章系统分析了这些药物的作用机制及临床疗效，并重点关注其颅内活性。曲妥珠单抗的引入使患者总生存期从单纯化疗的20.3个月延长至25.1个月。CLEOPATRA试验显示，帕妥珠单抗的联合应用进一步将生存期提升至57.1个月。在抗体偶联药物中，EMILIA试验表明T-DM1将总生存期从25.9个月提高至29.9个月；DESTINY-Breast03研究显示T-DXd将总生存期延长至52.6个月。T-DXd在活动性脑转移患者中展现出64.9%的客观缓解率，显示出显著的颅内活性。HER2CLIMB试验中，图卡替尼使活动性脑转移患者的颅内进展风险降低68%，总生存期从19.2个月提升至24.7个月。当前治疗已将中位总生存期从曲妥珠单抗问世前的约20个月提升至50个月以上。未来研究应聚焦于优化治疗序贯策略、完善生物标志物指导的治疗方案，并针对脑转移开发靶向治疗策略，以进一步提升患者的长期生存获益。

原文链接：

Impact of Anti-HER2 Therapies on Overall Survival in Patients with HER2-Positive Metastatic Breast Cancer: Focusing on Intracranial Efficacy of Emerging Treatments