Jourdain H, Di Meglio A, Mansouri I, Desplas D, Zureik M, Haddy N
EPI-PHARE, French National Agency for Medicine and Health Product Safety (ANSM) and the French National Health Insurance Center (CNAM), Saint-Denis.
Cancer Survivorship Program-INSERM Unit 981 Molecular Predictors and New Targets in Oncology-Gustave Roussy, Villejuif, France.
ESMO Open. 2024 Dec;9(12):104083. doi: 10.1016/j.esmoop.2024.104083. Epub 2024 Dec 10.
Since 2020, trastuzumab deruxtecan (T-DXd) has been used in France for patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive or HER2-low metastatic breast cancer (mBC). We aimed to describe the clinical characteristics, outcomes, and potential toxicities among patients receiving T-DXd for HER2-positive and HER2-low mBC.
Using the French National Health Data System (SNDS), we identified patients who initiated T-DXd for mBC from 30 September 2020 to 30 September 2023. Follow-up data were available through 31 December 2023. Patients were categorized into three groups according to HER2 expression and line of treatment: HER2-positive mBC receiving T-DXd in the third (HER2+ 3L) or second line (HER2+ 2L) and HER2-low mBC receiving T-DXd in the second line (HER2-low2L). We describe their characteristics and report the Kaplan-Meier estimates of overall survival (OS) and incidence of hospitalization.
The cohort comprised 5890 patients, including 2010 (34.1%) HER2+ 3L, 1260 (21.4%) HER2+ 2L, and 2620 (44.5%) HER2-low2L. For the three respective groups, the median age at inclusion was 59 years [interquartile range (IQR) 51-69 years], 59 years (50-68 years), and 61 years (52-70 years); 34.8%, 30.2%, and 16.0% had brain metastases; 14.2%, 13.7%, and 13.4% had a current or history of cardiovascular disease. Median OS was 30.2 months [95% confidence interval (CI) 28.1-33.5 months] for HER2+ 3L patients, was not reached for HER2+ 2L patients, and was 16.8 months (95% CI 14.5 months-not reached) for HER2-low2L patients. The incidence of hospitalization for cardiac, respiratory, digestive, and hematological disorders was similar for HER2-positive patients treated in the second or third line, whereas HER2-low patients had higher incidence rates for these events.
In this large French observational study, T-DXd users were older, had more comorbidities, and had more brain metastases than patients included in registration trials. The rapid expansion of clinical indications of T-DXd calls for proactive surveillance and timely management of potentially life-threatening T-DXd-related toxicity.
自2020年以来，曲妥珠单抗德曲妥珠单抗（T-DXd）在法国已用于先前接受过治疗的人表皮生长因子受体2（HER2）阳性或HER2低表达转移性乳腺癌（mBC）患者。我们旨在描述接受T-DXd治疗的HER2阳性和HER2低表达mBC患者的临床特征、结局和潜在毒性。
利用法国国家卫生数据系统（SNDS），我们确定了2020年9月30日至2023年9月30日开始使用T-DXd治疗mBC的患者。随访数据截至2023年12月31日。根据HER2表达和治疗线别将患者分为三组：接受三线（HER2+ 3L）或二线（HER2+ 2L）T-DXd治疗的HER2阳性mBC，以及接受二线T-DXd治疗的HER2低表达mBC（HER2-low2L）。我们描述了他们 的特征，并报告了总生存期（OS）的Kaplan-Meier估计值和住院发生率。
该队列包括5890例患者，其中2010例（34.1%）为HER2+ 3L，1260例（21.4%）为HER2+ 2L，2620例（44.5%）为HER2-low2L。对于这三组患者，纳入时的中位年龄分别为59岁[四分位间距（IQR）51 - 69岁]、59岁（50 - 68岁）和61岁（52 - 70岁）；34.8%、30.2%和16.0%有脑转移；14.2%、13.7%和13.4%有心血管疾病史或目前患有心血管疾病。HER2+ 3L患者的中位OS为30.2个月[95%置信区间（CI）28.1 - 33.5个月]，HER2+ 2L患者未达到，HER2-low2L患者为16.8个月（95% CI 14.5个月 - 未达到）。二线或三线接受治疗的HER2阳性患者因心脏、呼吸、消化和血液系统疾病住院的发生率相似，而HER2低表达患者这些事件的发生率更高。
在这项大型法国观察性研究中，与注册试验中的患者相比，使用T-DXd的患者年龄更大，合并症更多，脑转移更多。T-DXd临床适应症的迅速扩大要求对潜在危及生命的T-DXd相关毒性进行积极监测和及时管理。
