Single-agent lapatinib for HER2-overexpressing advanced or metastatic breast cancer that progressed on first- or second-line trastuzumab-containing regimens
Single-agent lapatinib for HER2-overexpressing advanced or metastatic breast cancer that progressed on first- or second-line trastuzumab-containing regimens
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DOI：
10.1093/annonc/mdn759
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发表时间：
2009-06-01
影响因子：
50.5
通讯作者：
Burstein, H. J.
中科院分区：
文献类型：
--
作者：
Blackwell, K. L.;Pegram, M. D.;Burstein, H. J.
背景资料：这项II期研究评估了拉帕替尼的疗效和安全性与人表皮生长因子受体2（HER 2）阳性的晚期或转移性乳腺癌患者的进展，在以前的trastuzumab therapy.Patients和方法：妇女与IIIB/IV期HER 2过度表达乳腺癌与单药拉帕替尼1250或1500毫克，每天一次治疗方案修订后。根据RECIST每8周评估一次肿瘤缓解。采用免疫组化和FISH技术检测肿瘤组织中HER 2的表达。研究者和独立审查的反应率[完全反应（CR）或部分反应（PR）]分别为7.7%和5.1%，临床获益率（CR、PR或病情稳定≥ 24周）分别为14.1%和9.0%。独立审查的中位进展时间为15.3周，中位总生存期为79周。最常见的治疗相关不良事件为皮疹（47%）、腹泻（46%）、恶心（31%）和疲劳（18%）。结论：拉帕替尼单药治疗HER 2过度表达乳腺癌（在含曲妥珠单抗治疗后进展）具有临床活性，且毒性作用可控。在转移性和早期乳腺癌中，有必要进行基于拉帕替尼的联合化疗方案和其他靶向治疗的研究。
Background: This phase II study evaluated the efficacy and safety of lapatinib in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic breast cancer that progressed during prior trastuzumab therapy.Patients and methods: Women with stage IIIB/IV HER2-overexpressing breast cancer were treated with single-agent lapatinib 1250 or 1500 mg once daily after protocol amendment. Tumor response according to RECIST was assessed every 8 weeks. HER2 expression was assessed in tumor tissue by immunohistochemistry and FISH.Results: Seventy-eight patients were enrolled in the study. Investigator and independent review response rates [complete response (CR) or partial response (PR)] were 7.7% and 5.1%, and clinical benefit rates (CR, PR, or stable disease for >= 24 weeks) were 14.1% and 9.0%, respectively. Median time to progression was 15.3 weeks by independent review, and median overall survival was 79 weeks. The most common treatment-related adverse events were rash (47%), diarrhea (46%), nausea (31%), and fatigue (18%).Conclusions: Single-agent lapatinib has clinical activity with manageable toxic effects in HER2-overexpressing breast cancer that progressed on trastuzumab-containing therapy. Studies of lapatinib-based combination regimens with chemotherapy and other targeted therapies in metastatic and earlier stages of breast cancer are warranted.