在一个大型转移性乳腺癌患者真实世界数据库中，根据生物标志物状态、治疗线数和既往是否接受过戈沙妥珠单抗，分析曲妥珠单抗德鲁替康的治疗结果。

Outcomes with trastuzumab deruxtecan by biomarker status, line of treatment and prior receipt of sacituzumab govitecan in a large real-world database of patients with metastatic breast cancer.

作者信息

Tarantino P, Lee D, Foldi J, Soulos P R, Gross C P, Grinda T, Winer E P, Lin N U, Krop I E, Tolaney S M, Lustberg M, Sammons S

机构信息

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, USA; Harvard Medical School, Boston, USA; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.

Yale School of Medicine, New Haven, USA.

出版信息

ESMO Open. 2025 Jun 17;10(7):105330. doi: 10.1016/j.esmoop.2025.105330.

DOI:10.1016/j.esmoop.2025.105330

PMID:40532362

Abstract

BACKGROUND

Most of the published data with trastuzumab deruxtecan (T-DXd) derive from clinical trials with selected populations and little representation of US patients. Limited real-world data are available.

PATIENTS AND METHODS

Using a nationwide electronic health record-derived database, we identified patients with metastatic breast cancer (MBC) who initiated T-DXd between December 2019 and September 2023. Tumors were categorized as human epidermal growth factor receptor 2 (HER2)-positive if positive at any time before starting T-DXd and HER2-negative if never HER2-positive before T-DXd. Hormone receptor (HR) status was derived from the last biopsy before T-DXd initiation. Real-world progression-free survival (rwPFS) and overall survival (OS) were estimated using the Kaplan-Meier method.

RESULTS

Overall, 1490 patients were included: 884 with HER2-positive, 487 with HR-positive/HER2-negative, and 119 with HR-negative/HER2-negative (triple-negative) MBC. Median age was 59 years (range 23-84 years), and median prior lines of systemic treatments were 3 and 4 for HER2-positive and HER2-negative MBC, respectively. rwPFS and OS were 12.3 and 24.6 months for HER2-positive disease; 7.6 and 15.5 months for HR-positive/HER2-negative disease; and 4.3 and 10.4 months for triple-negative disease. T-DXd use in earlier lines of treatment was associated with significantly longer rwPFS in HER2-positive (P = 0.02), but not in HR-positive/HER2-negative MBC (P = 0.07). Among patients with triple-negative disease pretreated with sacituzumab govitecan (SG, n = 58), after adjusting for prior lines of treatment, shorter rwPFS (3.4 versus 5.7 months, P = 0.009) and OS (9.0 versus 14.5 months, P = 0.002) were observed compared with patients without prior SG (n = 61). rwPFS with T-DXd was also significantly shorter in patients with BRCA mutations (7.8 versus 9.2 months, P = 0.02) and numerically shorter in patients with programmed death-ligand 1-negative disease (6.9 versus 12.6 months, P = 0.31).

CONCLUSIONS

In a large dataset, T-DXd showed favorable activity for treating MBC, although outcomes for HER2-positive disease appeared worse than those observed in clinical trials. Prior SG treatment was associated with inferior outcomes with T-DXd, suggesting cross-resistance between these antibody-drug conjugates.

摘要

背景

大多数已发表的关于曲妥珠单抗德瓦鲁单抗（T-DXd）的数据来自针对特定人群的临床试验，美国患者的代表性不足。可用的真实世界数据有限。

患者和方法

使用全国性电子健康记录衍生数据库，我们识别出在2019年12月至2023年9月期间开始使用T-DXd的转移性乳腺癌（MBC）患者。在开始使用T-DXd之前的任何时间呈阳性的肿瘤被分类为人表皮生长因子受体2（HER2）阳性，而在T-DXd之前从未呈HER2阳性的肿瘤被分类为HER2阴性。激素受体（HR）状态来自T-DXd开始前的最后一次活检。使用Kaplan-Meier方法估计真实世界无进展生存期（rwPFS）和总生存期（OS）。

结果

总体而言，纳入了1490例患者：884例HER2阳性、487例HR阳性/HER2阴性和119例HR阴性/HER2阴性（三阴性）MBC。中位年龄为59岁（范围23 - 84岁） HER2阳性和HER2阴性MBC的既往全身治疗中位线数分别为3和4。HER2阳性疾病的rwPFS和OS分别为12.3个月和24.6个月；HR阳性/HER2阴性疾病为7.6个月和15.5个月；三阴性疾病为4.3个月和10.4个月。在HER2阳性患者中，在早期治疗线中使用T-DXd与显著更长的rwPFS相关（P = 0.02），但在HR阳性/HER2阴性MBC中不相关（P = 0.07）。在接受过戈沙妥珠单抗（SG）预处理的三阴性疾病患者中（n = 58），在调整既往治疗线数后，与未接受过SG的患者（n = 61）相比，观察到rwPFS更短（3.4对5.7个月，P = 0.009）和OS更短（9.0对14.5个月，P = 0.002）。携带BRCA突变的患者使用T-DXd的rwPFS也显著更短（7.8对9.2个月，P = 0.02），程序性死亡配体1阴性疾病患者的rwPFS在数值上更短（6.9对12.6个月，P = 0.31）。