Neoadjuvant treatment with docetaxel plus lapatinib, trastuzumab, or both followed by an anthracycline-based chemotherapy in HER2-positive breast cancer: results of the randomised phase II EORTC 10054 study
Neoadjuvant treatment with docetaxel plus lapatinib, trastuzumab, or both followed by an anthracycline-based chemotherapy in HER2-positive breast cancer: results of the randomised phase II EORTC 10054 study
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DOI：
10.1093/annonc/mdu551
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发表时间：
2015-02-01
影响因子：
50.5
通讯作者：
Cameron, D.
中科院分区：
文献类型：
--
作者：
Bonnefoi, H.;Jacot, W.;Cameron, D.
背景资料：使用拉帕替尼和曲妥珠单抗双重HER2阻断剂联合不同的含紫杉醇化疗方案进行的新辅助治疗试验显示了较高的病理学完全缓解（pCR）率，但以严重毒性为代价。我们假设这种毒性可能是由于紫杉醇和拉帕替尼之间的特定相互作用。本试验评估的毒性和活性的多西他赛与拉帕替尼和trastuzumab. Patients和方法的组合：患者与IIA至IIIC期HER2阳性乳腺癌接受了6个周期的化疗（3个周期的多西他赛，其次是3个周期的氟尿嘧啶，表阿霉素，环磷酰胺）。他们被随机分配1：一曰：1例患者在前3个周期内接受拉帕替尼（每日口服1000 mg）、曲妥珠单抗（4 mg/kg负荷剂量，随后每周2 mg/kg）或曲妥珠单抗+拉帕替尼（相同剂量）。主要终点为pCR率，定义为ypT0/is。次要终点包括安全性和毒性。pCR率定义为ypT0/is ypN0，作为探索性分析进行评估。2012年6月，A组根据其他研究的结果因无效而关闭。结果：从2010年10月至2013年1月，128例患者纳入14个中心。拉帕替尼+曲妥珠单抗组中122例乳腺pCR以及乳腺和淋巴结pCR的可评估患者百分比在数值上最高（分别为60%和56%），曲妥珠单抗组居中（52%和52%），拉帕替尼组最低（46%和36%）。拉帕替尼/曲妥珠单抗/拉帕替尼+曲妥珠单抗组中最常见的3 - 4级毒性的频率（%）为：发热性中性粒细胞减少症23/15/10、腹泻9/2/18、感染（其他）9/4/8和肝脏毒性0/2/8。结论：这项研究表明，双重抗HER2阻断加化疗在数值上适度增加pCR率，但表明使用多西他赛而不是紫杉醇可能不会降低毒性。
Background: Neoadjuvant trials conducted using a double HER2 blockade with lapatinib and trastuzumab, combined with different paclitaxel-containing chemotherapy regimens, have shown high pathological complete response (pCR) rates, but at the cost of important toxicity. We hypothesised that this toxicity might be due to a specific interaction between paclitaxel and lapatinib. This trial assesses the toxicity and activity of the combination of docetaxel with lapatinib and trastuzumab.Patients and methods: Patients with stage IIA to IIIC HER2-positive breast cancer received six cycles of chemotherapy (three cycles of docetaxel followed by three cycles of fluorouracil, epirubicin, cyclophosphamide). They were randomised 1 : 1 : 1 to receive during the first three cycles either lapatinib (1000 mg orally daily), trastuzumab (4 mg/kg loading dose followed by 2 mg/kg weekly), or trastuzumab + lapatinib at the same dose. The primary end point was pCR rate defined as ypT0/is. Secondary end points included safety and toxicity. pCR rate defined as ypT0/is ypN0 was assessed as an exploratory analysis. In June 2012, arm Awas closed for futility based on the results from other studies.Results: From October 2010 to January 2013, 128 patients were included in 14 centres. The percentage of the 122 assessable patients with pCR in the breast, and pCR in the breast and nodes, was numerically highest in the lapatinib + trastuzumab group (60% and 56%, respectively), intermediate in the trastuzumab group (52% and 52%), and lowest in the lapatinib group (46% and 36%). Frequency (%) of the most common grade 3-4 toxicities in the lapatinib /trastuzumab/lapatinib + trastuzumab arms were: febrile neutropenia 23/15/10, diarrhoea 9/2/18, infection (other) 9/4/8, and hepatic toxicity 0/2/8.Conclusions: This study demonstrates a numerically modest pCR rate increase with double anti-HER2 blockade plus chemotherapy, but suggests that the use of docetaxel rather than paclitaxel may not reduce toxicity.