Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: Results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer
Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: Results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer
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DOI：
10.1200/jco.2005.07.032
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发表时间：
2005-06-01
影响因子：
45.3
通讯作者：
Hortobagyi, GN
中科院分区：
文献类型：
--
作者：
Buzdar, AU;Ibrahim, NK;Hortobagyi, GN
目的本研究的目的是确定在新辅助化疗中加入曲妥珠单抗是否可以增加人表皮生长因子受体2（HER2）阳性疾病患者的病理完全缓解（pCR）率。可手术乳腺癌的阳性疾病被随机分配到四个周期的紫杉醇，随后是四个周期的氟尿嘧啶，表阿霉素，和环磷酰胺或相同的化疗与同时每周曲妥珠单抗24周。主要目的是证明在化疗中添加曲妥珠单抗后pCR改善20%（假设为21%至41%）。计划样本量为164例。结果两组患者的预后因素相似。在34名患者完成治疗后，试验的数据监测委员会停止了试验，因为曲妥珠单抗联合化疗的优越性。化疗组（n = 16）和曲妥珠单抗联合化疗组（n = 18）的pCR率分别为25%和66.7%（P = 0.02）。该决定基于以下计算：如果研究继续纳入164例患者，则曲妥珠单抗联合化疗具有上级优效性的概率为95%。在42例随机化患者中，化疗组26%达到pCR，而曲妥珠单抗+化疗组65.2%达到pCR（P = 0.016）。尽管未观察到临床充血性心力衰竭，但该方法的安全性尚未确定。在化疗和曲妥珠单抗加化疗armus.Conclusion，尽管样本量小，这些数据表明，增加曲妥珠单抗化疗，在本试验中使用，显着增加pCR无临床充血性心力衰竭的5和7例患者的心脏射血分数下降超过10%。
Purpose The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2)-positive disease.Patients and Methods Forty-two patients with HER2-positive disease with operable breast cancer were randomly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks. The primary objective was to demonstrate a 20% improvement in pCR (assumed 21% to 41%) with the addition of trastuzumab to chemotherapy. The planned sample size was 164 patients.Results Prognostic factors were similar in the two groups. After 34 patients had completed therapy, the trial's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy. pCR rates were 25% and 66.7% for chemotherapy (n = 16) and trastuzumab plus chemotherapy (n = 18), respectively (P =.02). The decision was based on the calculation that, if study continued to 164 patients, there was a 95% probability that trastuzumab plus chemotherapy would be superior. Of the 42 randomized patients, 26% in the chemotherapy arm achieved pCR compared with 65.2% in the trastuzumab plus chemotherapy arm (P = .016). The safety of this approach is not established, although no clinical congestive heart failure was observed. A more than 10% decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms, respectively.Conclusion Despite the small sample size, these data indicate that adding trastuzumab to chemotherapy, as used in this trial, significantly increased pCR without clinical congestive heart failure.