奥地利维也纳医科大学Matthias Preusser团队近期取得重要研究进展，他们进行了利用Trastuzumab deruxtecan治疗伴有脑转移的HER2阳性乳腺癌的单臂2期临床试验。相关研究结果2022年8月8日在线发表于《自然—医学》杂志上。

研究人员进行了前瞻性、公开标签、单臂、2期TUXEDO-1试验。研究团队招募了年龄≥18岁的HER2阳性乳腺癌和新诊断的未经治疗的脑转移或在先前的局部治疗后进展的脑转移患者，先前接触过曲妥珠单抗和帕妥珠单抗并且没有立即局部治疗。患者每3周一次以5.4mg/kg体重的标准剂量静脉内接受Trastuzumab deruxtecan。

主要终点是根据神经肿瘤学脑转移的疗效评估标准测量颅内缓解率。西蒙的两阶段设计被用来比较响应率<26%的无效假设和61%的备选假设。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%保密区间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试验中， Trastuzumab deruxtecan在HER2阳性乳腺癌脑转移患者中显示出较高的颅内缓解率，应被视为这种情况下的治疗选择。

据介绍，Trastuzumab 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的颅外活性。

附：英文原文

Title: Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial

Author: Bartsch, Rupert, Berghoff, Anna Sophie, Furtner, Julia, Marhold, Maximilian, Bergen, Elisabeth Sophie, Roider-Schur, Sophie, Starzer, Angelika Martina, Forstner, Heidrun, Rottenmanner, Beate, Dieckmann, Karin, Bago-Horvath, Zsuzsanna, Haslacher, Helmuth, Widhalm, Georg, Ilhan-Mutlu, Aysegl, Minichsdorfer, Christoph, Fuereder, Thorsten, Szekeres, Thomas, Oehler, Leopold, Gruenberger, Birgit, Singer, Christian F., Weltermann, Ansgar, Puhr, Rainer, Preusser, Matthias

Issue&Volume: 2022-08-08

Abstract: 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 ≥18years 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 5.4mg per kg bodyweight once every 3weeks. 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.

DOI: 10.1038/s41591-022-01935-8

Source: https://www.nature.com/articles/s41591-022-01935-8