曲妥珠单抗deruxtecan (DS-8201a)用于先前接受曲妥珠单抗emtansine治疗的晚期her2阳性乳腺癌患者:一项剂量扩大的一期研究。

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田村K，鹤谷J，高桥S，岩田H, Krop IE, Redfern C, Sagara Y, Doi T, Park H, Murthy RK, Redman RA, Jikoh T, Lee C，杉原M, Shahidi J, Yver A, Modi S

曲妥珠单抗deruxtecan (DS-8201a)用于先前接受曲妥珠单抗emtansine治疗的晚期her2阳性乳腺癌患者:一项剂量扩大的一期研究。

《柳叶刀肿瘤学杂志》2019年6月;20(6):816-826。doi: 10.1016 / s1470 - 2045 (19) 30097 - x。2019年4月29日。

PubMed ID
31047803 (在PubMed
］
摘要

背景:曲妥珠单抗德鲁特康(DS-8201a)是一种新型her2靶向抗体药物偶联物，与人源化抗her2抗体、可裂解肽基连接剂和强效拓扑异构酶I抑制剂负载结合。一项1期、非随机、开放标签、多剂量研究评估了曲妥珠单抗在her2表达的晚期实体肿瘤中的安全性、耐受性和活性。剂量增加(第1部分)之前已经报道过，建议剂量增加为5.4 mg/kg或6.4 mg/kg。在这篇文章中，我们报道了这项1期试验的安全性和初步活性结果，所有her2阳性晚期乳腺癌患者既往曾接受曲妥珠单抗伊美坦辛治疗，并以推荐剂量接受曲妥珠单抗德鲁替康扩大治疗。方法:我们在美国的8家医院和诊所以及日本的6家医院和诊所进行了一项开放标签、剂量递增和剂量扩展的一期试验。符合条件的患者在美国至少18岁，在日本至少20岁，患有晚期实体瘤(无论剂量增加时HER2表达或剂量增加时HER2表达或突变)。建议剂量增加为5.4 mg/kg或6.4 mg/kg，每3周静脉给予患者一次曲妥珠单抗，直到撤回同意，不可接受的毒性，或疾病进展。在这篇文章中，所有her2阳性的晚期乳腺癌患者都曾接受过曲妥珠单抗伊美坦辛治疗，并按推荐剂量接受了曲妥珠单抗德鲁替康的扩大治疗。研究的主要终点是安全性和初步活动(根据研究人员的评估，达到客观反应的患者比例)。活度评估集包括所有按推荐剂量接受了至少一剂曲妥珠单抗的患者，这些患者的基线和治疗后活度数据都是可用的。 The safety analysis set included all patients who received at least one dose of trastuzumab deruxtecan at the recommended doses for expansion. Enrolment for patients with HER2-positive breast cancer has been completed. This trial is registered at ClinicalTrials.gov, number NCT02564900, and ClinicalTrials.jp, number JapicCTI-152978. FINDINGS: Between Aug 28, 2015, and Aug 10, 2018, 115 of 118 patients with HER2-positive breast cancer were treated with at least one dose of trastuzumab deruxtecan at the recommended doses for expansion. All patients had at least one treatment-emergent adverse event. Frequent grade 3 or worse treatment-emergent adverse events included anaemia (19 [17%] of 115) and decreased neutrophil (16 [14%]), white blood cell (ten [9%]), and platelet (nine [8%]) counts. At least one serious treatment-emergent adverse event occurred for 22 (19%) patients. Investigators reported 20 cases of interstitial lung disease, pneumonitis, or organising pneumonia, including one grade 3 event and two treatment-related deaths due to pneumonitis. One death unrelated to study treatment was due to progressive disease. 66 (59.5%; 95% CI 49.7-68.7) of 111 patients had a confirmed objective response. INTERPRETATION: Trastuzumab deruxtecan had a manageable safety profile and showed preliminary activity in trastuzumab emtansine-pretreated patients with HER2-positive breast cancer. These results suggest that further development in phase 2 and 3 clinical trials for HER2-positive breast cancer is warranted. FUNDING: Daiichi Sankyo Co, Ltd.

引用本文的药库数据

药物
药物靶点
药物 目标 种类 生物 药理作用 行动
曲妥珠单抗deruxtecan DNA拓扑异构酶1 蛋白质 人类
是的
抑制剂
 细节
曲妥珠单抗deruxtecan 高亲和力免疫球蛋白γ Fc受体I 蛋白质 人类
是的
抗体
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