达泊托单抗德鲁替康与化疗用于既往治疗过的不可切除/转移性激素受体阳性、人表皮生长因子受体2阴性乳腺癌的疗效比较：TROPION-Breast01研究的主要结果
Datopotamab Deruxtecan Versus Chemotherapy in Previously Treated Inoperable/Metastatic Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: Primary Results From TROPION-Breast01.
作者信息
Bardia Aditya, Jhaveri Komal, Im Seock-Ah, Pernas Sonia, De Laurentiis Michelino, Wang Shusen, Martínez Jañez Noelia, Borges Giuliano, Cescon David W, Hattori Masaya, Lu Yen-Shen, Hamilton Erika, Zhang Qingyuan, Tsurutani Junji, Kalinsky Kevin, Rubini Liedke Pedro Emanuel, Xu Lu, Fairhurst Rick M, Khan Sabrina, Denduluri Neelima, Rugo Hope S, Xu Binghe, Pistilli Barbara
机构信息
Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA.
Massachusetts General Hospital Cancer Center, Boston, MA.
出版信息
J Clin Oncol. 2025 Jan 20;43(3):285-296. doi: 10.1200/JCO.24.00920. Epub 2024 Sep 12.
PURPOSE
The global, phase 3, open-label, randomized TROPION-Breast01 study assessed the trophoblast cell surface antigen 2-directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) versus investigator's choice of chemotherapy (ICC) in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer.
METHODS
Adult patients with inoperable/metastatic HR+/HER2‒ breast cancer, who had disease progression on endocrine therapy, for whom endocrine therapy was unsuitable, and had received one to two previous lines of chemotherapy in the inoperable/metastatic setting, were randomly assigned 1:1 to Dato-DXd (6 mg/kg once every 3 weeks) or ICC (eribulin/vinorelbine/capecitabine/gemcitabine). Dual primary end points were progression-free survival (PFS) by blinded independent central review (BICR) and overall survival (OS).
RESULTS
Patients were randomly assigned to Dato-DXd (n = 365) or ICC (n = 367). Dato-DXd significantly reduced the risk of progression or death versus ICC (PFS by BICR hazard ratio [HR], 0.63 [95% CI, 0.52 to 0.76]; < .0001). Consistent PFS benefit was observed across subgroups. Although OS data were not mature, a trend favoring Dato-DXd was observed (HR, 0.84 [95% CI, 0.62 to 1.14]). The rate of grade ≥3 treatment-related adverse events (TRAEs) with Dato-DXd was lower than ICC (20.8% 44.7%). The most common TRAEs (any grade; grade ≥3) were nausea (51.1%; 1.4%) and stomatitis (50%; 6.4%) with Dato-DXd and neutropenia (grouped term, 42.5%; 30.8%) with ICC.
CONCLUSION
Patients receiving Dato-DXd had statistically significant and clinically meaningful improvement in PFS and a favorable and manageable safety profile, compared with ICC. Results support Dato-DXd as a novel treatment option for patients with inoperable/metastatic HR+/HER2‒ breast cancer who have received one to two previous lines of chemotherapy in this setting.
目的
全球3期开放标签随机TROPION-Breast01研究评估了滋养层细胞表面抗原2导向抗体药物偶联物达妥昔单抗德鲁替康（Dato-DXd）与研究者选择的化疗方案（ICC）用于激素受体阳性/人表皮生长因子受体2阴性（HR+/HER2-）乳腺癌的疗效。
方法
成年不可手术/转移性HR+/HER2-乳腺癌患者，在内分泌治疗中出现疾病进展、不适合内分泌治疗且在不可手术/转移性情况下接受过1至2线化疗，按1:1随机分配至Dato-DXd组（6 mg/kg，每3周1次）或ICC组（艾日布林/长春瑞滨/卡培他滨/吉西他滨）。双主要终点为经盲法独立中央审查（BICR）评估的无进展生存期（PFS）和总生存期（OS）。
结果
患者被随机分配至Dato-DXd组（n = 365）或ICC组（n = 367）。与ICC相比，Dato-DXd显著降低了疾病进展或死亡风险（BICR评估的PFS风险比[HR]，0.63[95%CI，0.52至0.76]；P <.0001）。在各亚组中均观察到一致的PFS获益。虽然OS数据不成熟，但观察到有利于Dato-DXd的趋势（HR，0.84[95%CI，0.62至1.14]）。Dato-DXd组≥3级治疗相关不良事件（TRAEs）发生率低于ICC组（20.8%对44.7%）。Dato-DXd组最常见的TRAEs（任何级别；≥3级）为恶心（51.1%；1.4%）和口腔炎（50%；6.4%），ICC组为中性粒细胞减少（合并术语，42.5%；30.8%）。
结论
与ICC相比，接受Dato-DXd治疗的患者在PFS方面有统计学显著且具有临床意义的改善，且安全性良好且可控。结果支持Dato-DXd作为不可手术/转移性HR+/HER2-乳腺癌患者在该情况下接受过1至2线化疗后的一种新型治疗选择。
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