Background/Objectives: Breast cancer is the most common malignant neoplasm in women and the leading cause of cancer-related death. Approximately 50% of HER2-negative breast cancers exhibit low expression of this protein (HER2-low). Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate targeting the HER2 receptor which has shown benefit in patients with HER2-low metastatic breast cancer in the DESTINY-Breast04 study. However, few data are available on its efficacy in real-world practice.Methods: We conducted a retrospective multicenter national study (eight centers) including patients with advanced HER2-low breast cancer (immunohistochemistry 1+ or 2+/ in situ hybridization negative) who started T-DXd treatment between January 2022 and March 2024. Patients had received at least one previous line of treatment. The primary endpoint was real-world progression-free survival (rwPFS) in patients with metastatic HER2-low breast cancer treated with T-DXd. The secondary endpoints were real-world overall survival (OS) and objective response rate (ORR).Results: The study included 35 patients (34 female and 1 male patient), with a median age of 54 years at the start of T-DXd. All patients had an ECOG-PS 0–1, and 26 patients (74%) had hormone receptor (HR)-positive disease. The median number of prior lines of treatment was 4 [1–7], and 23 patients (65.8%) had metastases in three or more sites. With a median follow-up of 7.8 months, rwPFS was 6 months (95% CI, 2.3–9.7), and OS was 15 months (95% CI, 4.7–25.3). In HR-positive patients, the median rwPFS was 6 months (95% CI, 1.2–10.7), compared to 4 months (95% CI, 2.1–5.9) in HR-negative patients. The overall ORR was 52.9%. Adverse events of grade 3 or higher were neutropenia (2.9%) and fatigue (2.9%).Conclusions: This study provides real-world data on T-DXd in the treatment of advanced HER2-low breast cancer. It is noteworthy that the population was heavily pre-treated and had a higher proportion of HR-negative patients, which may explain the lower efficacy compared to the DESTINY-Breast04 study.
背景/目的：乳腺癌是女性最常见的恶性肿瘤，也是癌症相关死亡的主要原因。约50%的HER2阴性乳腺癌存在该蛋白低表达（HER2-low）。Trastuzumab deruxtecan（T-DXd）是一种靶向HER2受体的抗体偶联药物，在DESTINY-Breast04研究中显示出对HER2低表达转移性乳腺癌患者的获益。然而，其在真实世界实践中的疗效数据仍较为有限。 方法：我们开展了一项全国性多中心回顾性研究（纳入8个中心），纳入2022年1月至2024年3月期间开始接受T-DXd治疗的晚期HER2低表达乳腺癌患者（免疫组化1+或2+/原位杂交阴性）。所有患者既往至少接受过一线治疗。主要终点为接受T-DXd治疗的转移性HER2低表达乳腺癌患者的真实世界无进展生存期（rwPFS）。次要终点包括真实世界总生存期（OS）和客观缓解率（ORR）。 结果：研究共纳入35例患者（34例女性，1例男性），开始T-DXd治疗时的中位年龄为54岁。所有患者ECOG-PS评分为0-1分，其中26例（74%）为激素受体（HR）阳性。患者既往接受治疗线数的中位数为4线[范围1-7线]，23例患者（65.8%）存在三个或更多部位的转移。中位随访7.8个月后，rwPFS为6个月（95% CI，2.3-9.7），OS为15个月（95% CI，4.7-25.3）。在HR阳性患者中，中位rwPFS为6个月（95% CI，1.2-10.7），而HR阴性患者为4个月（95% CI，2.1-5.9）。总体ORR为52.9%。3级及以上不良事件包括中性粒细胞减少症（2.9%）和疲劳（2.9%）。 结论：本研究提供了T-DXd治疗晚期HER2低表达乳腺癌的真实世界数据。值得注意的是，该研究人群既往接受过大量治疗且HR阴性患者比例较高，这可能是其疗效低于DESTINY-Breast04研究的原因。
肿瘤(癌症)患者之家