Trastuzumab deruxtecan is an antibody–drug conjugate with high extracranial activity in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. We conducted the prospective, open-label, single-arm, phase 2 TUXEDO-1 trial. We enrolled patients aged ≥18 years with HER2-positive breast cancer and newly diagnosed untreated brain metastases or brain metastases progressing after previous local therapy, previous exposure to trastuzumab and pertuzumab and no indication for immediate local therapy. Patients received trastuzumab deruxtecan intravenously at the standard dose of 5.4 mg per kg bodyweight once every 3 weeks. The primary endpoint was intracranial response rate measured according to the response assessment in neuro-oncology brain metastases criteria. A Simon two-stage design was used to compare a null hypothesis of <26% response rate against an alternative of 61%. Fifteen patients were enrolled in the intention-to-treat population of patients who received at least one dose of study drug. Two patients (13.3%) had a complete intracranial response, nine (60%) had a partial intracranial response and three (20%) had stable disease as the best intracranial response, with a best overall intracranial response rate of 73.3% (95% confidential interval 48.1–89.1%), thus meeting the predefined primary outcome. No new safety signals were observed and global quality-of-life and cognitive functioning were maintained over the treatment duration. In the TUXEDO-1 trial (NCT04752059, EudraCT 2020-000981-41), trastuzumab deruxtecan showed a high intracranial response rate in patients with active brain metastases from HER2-positive breast cancer and should be considered as a treatment option in this setting.

曲妥珠单抗 deruxtecan 是一种抗体-药物偶联物，在人表皮生长因子受体 2 (HER2) 阳性转移性乳腺癌中具有高颅外活性。我们进行了前瞻性、开放标签、单臂、2 期 TUXEDO-1 试验。我们招募了年龄≥18 岁的 HER2 阳性乳腺癌和新诊断的未经治疗的脑转移瘤或在先前局部治疗、先前暴露于曲妥珠单抗和帕妥珠单抗且没有立即局部治疗指征后进展的脑转移瘤的患者。患者每 3 周一次以 5.4 mg/kg 体重的标准剂量静脉内接受曲妥珠单抗 deruxtecan。主要终点是根据神经肿瘤学脑转移标准中的反应评估测量的颅内反应率。使用 Simon 两阶段设计来比较 < 26% 的响应率与 61% 的替代方案相比。15 名患者被纳入接受至少一剂研究药物的意向治疗人群。2例（13.3%）颅内完全缓解，9例（60%）颅内部分缓解，3例（20%）病情稳定为最佳颅内缓解，最佳总体颅内缓解率为73.3%（95%）机密区间 48.1-89.1%），从而满足预定义的主要结果。没有观察到新的安全信号，并且在治疗期间维持了整体生活质量和认知功能。在 TUXEDO-1 试验（NCT04752059，EudraCT 2020-000981-41）中，