Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Paseo Vall d'Hebron 119-129, Barcelona, Spain E-08035.
J Clin Oncol. 2010 Mar 1;28(7):1138-44. doi: 10.1200/JCO.2009.24.2024. Epub 2010 Feb 1.
PURPOSE; Pertuzumab, a human epidermal growth factor receptor 2 (HER2) -targeted monoclonal antibody, potently inhibits HER2 dimerization and HER-mediated signaling pathways. Pertuzumab and the approved HER2-targeted monoclonal antibody trastuzumab have complementary mechanisms of action and result in enhanced antitumor activity when combined. This phase II trial assessed the efficacy and safety profile of the combination in patients with HER2-positive breast cancer whose disease had progressed during prior trastuzumab-based therapy.
This was a multicenter, open-label, single-arm, Simon two-stage study. Patients with advanced HER2-positive breast cancer in whom disease progression had occurred during prior trastuzumab-based therapy received trastuzumab weekly (4 mg/kg loading dose, then 2 mg/kg every week) or every 3 weeks (8 mg/kg loading dose, then 6 mg/kg every 3 weeks) and pertuzumab every 3 weeks (840 mg loading dose, then 420 mg every 3 weeks). Treatment continued until disease progression or excessive toxicity.
All 66 patients were assessable for efficacy and safety. The objective response rate was 24.2%, and the clinical benefit rate was 50%. Five patients (7.6%) experienced a complete response, 11 patients (16.7%) experienced a partial response, and 17 patients (25.8%) experienced stable disease of > or = 6 months. Median progression-free survival was 5.5 months. Overall, the combination of pertuzumab and trastuzumab was well tolerated, and adverse events were mild to moderate. Cardiac dysfunction was minimal, and no patients withdrew as a result of cardiac-related adverse events.
The combination of pertuzumab and trastuzumab is active and well tolerated in patients with metastatic HER2-positive breast cancer who had experienced progression during prior trastuzumab therapy.
帕妥珠单抗是一种人表皮生长因子受体 2（HER2）靶向单克隆抗体，能够强效抑制 HER2 二聚化和 HER 介导的信号通路。帕妥珠单抗与已获批的 HER2 靶向单克隆抗体曲妥珠单抗具有互补的作用机制，当联合使用时可增强抗肿瘤活性。本 II 期临床试验评估了该联合方案在既往曲妥珠单抗治疗期间疾病进展的 HER2 阳性乳腺癌患者中的疗效和安全性。
这是一项多中心、开放标签、单臂、Simon 两阶段研究。既往曲妥珠单抗治疗期间疾病进展的晚期 HER2 阳性乳腺癌患者接受曲妥珠单抗每周（4 mg/kg 负荷剂量，然后每周 2 mg/kg）或每 3 周（8 mg/kg 负荷剂量，然后每 3 周 6 mg/kg）和帕妥珠单抗每 3 周（840 mg 负荷剂量，然后每 3 周 420 mg）治疗。治疗持续至疾病进展或毒性不可耐受。
所有 66 例患者均可进行疗效和安全性评估。客观缓解率为 24.2%，临床获益率为 50%。5 例患者（7.6%）出现完全缓解，11 例患者（16.7%）出现部分缓解，17 例患者（25.8%）出现≥6 个月的疾病稳定。中位无进展生存期为 5.5 个月。总体而言，帕妥珠单抗联合曲妥珠单抗耐受性良好，不良反应为轻至中度。心脏功能障碍轻微，无患者因心脏相关不良反应而停药。
在既往曲妥珠单抗治疗期间进展的转移性 HER2 阳性乳腺癌患者中，帕妥珠单抗联合曲妥珠单抗具有活性且耐受性良好。
