德曲妥珠单抗在HER2阳性及HER2低表达晚期乳腺癌中的疗效与安全性：一项单中心真实世界研究<sup>★</sup>

doi:10.3969/j.issn.2095-1264.2025.04.01

首页 > 过刊浏览>2025年第4期 >433-443. DOI:10.3969/j.issn.2095-1264.2025.04.01

德曲妥珠单抗在HER2阳性及HER2低表达晚期乳腺癌中的疗效与安全性：一项单中心真实世界研究★
DOI:
                        10.3969/j.issn.2095-1264.2025.04.01
                    
作者:
                        
                        
                    
作者单位:湖南省肿瘤医院/中南大学湘雅医学院附属肿瘤医院 乳腺内科，湖南 长沙，410013
作者简介:刘斌亮，男，博士，主治医师，研究方向为乳腺恶性肿瘤的内科诊治及临床转化。
通讯作者:欧阳取长，男，博士，主任医师，研究方向为乳腺恶性肿瘤的内科诊治及临床转化。
中图分类号:R737.9;R730.51
基金项目:湖南省自然科学基金资助项目（2023JJ60464）；湖南省自然科学基金青年基金资助项目（2024JJ6289）；长沙市自然科学基金资助项目（kq2403120）；湖南省肿瘤医院攀登计划资助项目（ZX2021005）；湖南省肿瘤医院攀登计划启航基金资助项目（QH2023006）；湖南省肿瘤医院高层次人才五年行动计划支持（20250731-1050）。

Efficacy and safety of trastuzumab deruxtecan in HER2-positive and HER2-low metastatic breast cancer: a single-center real-world study^★

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Affiliation:

Department of Breast Cancer Internal Medical, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China

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摘要:

目的评估德曲妥珠单抗（T-DXd）治疗人表皮生长因子受体2（HER2）阳性及HER2低表达晚期乳腺癌患者的真实世界疗效与安全性，并探讨预后影响因素。方法纳入2022年4月—2024年8月湖南省肿瘤医院乳腺内科接受T-DXd治疗的144例晚期乳腺癌患者，其中HER2阳性86例（59.7%），HER2低表达58例（40.3%）。根据RECIST v1.1每2周期评估疗效，采用Kaplan-Meier法估算中位无进展生存期（PFS），Cox比例风险模型分析预后危险因素。结果所有入组患者中位年龄53.0岁，内脏转移率87.5%。中位治疗线数3线，客观缓解率（ORR）38.2%，疾病控制率（DCR）89.6%，中位PFS为8.93个月（95% CI： 7.70~13.20）。HER2阳性组较HER2低表达组显示出更优的ORR（44.2% vs. 29.3%）及中位PFS（13.20个月vs. 6.70个月）（P<0.001）。多因素分析显示，HER2阳性组ECOG评分≥1分（HR=3.109， P=0.004）与既往抗HER2治疗（HR=4.934， P=0.002）是PFS的独立危险因素；HER2低表达组紫杉类化疗史（HR=5.133， P=0.017）及HER2异质性（HR=2.363， P=0.022）与不良预后相关，而既往化疗线数>3线与较长的PFS相关（HR=0.333， P=0.045）。安全性方面，最常见的不良反应为天冬氨酸转氨酶（AST）升高（63.9%）、中性粒细胞减少（58.3%）及白细胞减少（57.6%），≥3级不良事件发生率较低（中性粒细胞减少7.0%，血小板减少2.3%）。间质性肺炎（ILD）发生率为3.5%，其中2例（1.4%）为3级事件。结论 T-DXd在真实世界中治疗HER2阳性及低表达晚期乳腺癌均具有明确疗效，其中HER2阳性患者获益更显著。ECOG评分、治疗史及HER2表达状态等是影响患者预后的关键因素。临床实践中需结合分子特征及治疗背景优化治疗方案，并重点监测血液学毒性及ILD等严重不良事件。

Abstract:

Objective To evaluate the real-world efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-positive and HER2-low expression advanced breast cancer, and to explore prognostic factors.Methods A total of 144 patients with advanced breast cancer who received T-DXd treatment at the Department of Medical Oncology, Hunan Cancer Hospital, from April 2022 to August 2024 were included. Among them, 86 patients (59.7%) had HER2-positive disease and 58 (40.3%) had HER2-low expression. Treatment response was assessed every two cycles according to RECIST v1.1. Median progression-free survival (PFS) was estimated using the Kaplan-Meier method, and prognostic factors were analyzed using the Cox proportional hazards model.Results The median age of all enrolled patients was 53.0 years, and 87.5% had visceral metastases. The median number of prior lines of therapy was three. The objective response rate (ORR) was 38.2%, and the disease control rate (DCR) was 89.6%. The median PFS was 8.93 months (95% CI: 7.70-13.20). Compared with the HER2-low group, the HER2-positive group demonstrated superior ORR (44.2% vs. 29.3%) and median PFS (13.20 months vs. 6.70 months) (P<0.001). Multivariate analysis revealed that among HER2-positive patients, ECOG performance status ≥1 (HR=3.109, P=0.004) and prior anti-HER2 therapy (HR=4.934, P=0.002) were independent risk factors for shorter PFS. Among HER2-low patients, a history of taxane chemotherapy (HR=5.133, P=0.017) and HER2 heterogeneity (HR=2.363, P=0.022) were associated with poor prognosis, while receiving more than three lines of chemotherapy was associated with longer PFS (HR=0.333, P=0.045). Regarding safety, The most common adverse events were elevated aspartate aminotransferase (AST) (63.9%), neutropenia (58.3%), and leukopenia (57.6%). The incidence of grade ≥3 adverse events was relatively low (neutropenia 7.0%, thrombocytopenia 2.3%). The incidence of interstitial lung disease (ILD) was 3.5%, including two grade 3 events (1.4%).Conclusion T-DXd demonstrated substantial real-world efficacy in both HER2-positive and HER2-low advanced breast cancer, with greater benefit observed in HER2-positive patients. ECOG performance status, treatment history, and HER2 expression level were key prognostic factors. In clinical practice, individualized treatment strategies should be developed based on molecular characteristics and prior therapy, with close monitoring for hematologic toxicities and ILD.