BACKGROUND Neoadjuvant dual human epidermal growth factor receptor (HER2) blockade with trastuzumab and pertuzumab plus paclitaxel leads to an overall pathologic complete response (pCR) rate of 46%. Dual HER2 blockade with ado-trastuzumab emtansine (T-DM1) and lapatinib plus nab-paclitaxel has shown efficacy in patients with metastatic HER2-positive breast cancer. To test neoadjuvant effectiveness of this regimen, an open-label, multicenter, randomized, phase II trial was conducted comparing T-DM1, lapatinib, and nab-paclitaxel with trastuzumab, pertuzumab, and paclitaxel in patients with early-stage HER2-positive breast cancer. METHODS Stratification by estrogen receptor (ER) status occurred prior to randomization. Patients in the experimental arm received 6 weeks of targeted therapies (T-DM1 and lapatinib) followed by T-DM1 every 3 weeks, lapatinib daily, and nab-paclitaxel weekly for 12 weeks. In the standard arm, patients received 6 weeks of trastuzumab and pertuzumab followed by trastuzumab weekly, pertuzumab every 3 weeks, and paclitaxel weekly for 12 weeks. The primary objective was to evaluate the proportion of patients with residual cancer burden (RCB) 0 or I. Key secondary objectives included pCR rate, safety, and change in tumor size at 6 weeks. Hypothesis-generating correlative assessments were also performed. RESULTS The 30 evaluable patients were well-balanced in patient and tumor characteristics. The proportion of patients with RCB 0 or I was higher in the experimental arm (100% vs. 62.5% in the standard arm, p = 0.0035). In the ER-positive subset, all patients in the experimental arm achieved RCB 0-I versus 25% in the standard arm (p = 0.0035). Adverse events were similar between the two arms. CONCLUSION In early-stage HER2-positive breast cancer, the neoadjuvant treatment with T-DM1, lapatinib, and nab-paclitaxel was more effective than the standard treatment, particularly in the ER-positive cohort. TRIAL REGISTRATION Clinicaltrials.gov NCT02073487 , February 27, 2014.

中文翻译：

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HER2阳性乳腺癌新辅助治疗的阿托曲妥珠单抗氨丹宁，拉帕替尼和nab紫杉醇与曲妥珠单抗，帕妥珠单抗和紫杉醇的II期随机对照对照试验（TEAL研究）。

背景技术用曲妥珠单抗和帕妥珠单抗加紫杉醇的新辅助双重人表皮生长因子受体（HER2）阻断可导致46％的总体病理完全缓解（pCR）率。用阿杜曲妥珠单抗（T-DM1）和拉帕替尼加纳布-紫杉醇双重HER2阻断剂对转移性HER2阳性乳腺癌患者显示出疗效。为了测试该方案的新辅助疗效，进行了一项开放性，多中心，随机，II期试验，比较了早期HER2阳性乳腺癌患者中的T-DM1，拉帕替尼和纳布-紫杉醇与曲妥珠单抗，帕妥珠单抗和紫杉醇癌症。方法根据雌激素受体（ER）状态进行分层，然后进行随机分组。实验组的患者接受了6周的靶向治疗（T-DM1和拉帕替尼），随后每3周接受T-DM1，每天使用拉帕替尼，每周12个月用nab-紫杉醇。在标准组中，患者接受曲妥珠单抗和帕妥珠单抗治疗6周，然后每周接受曲妥珠单抗治疗，每3周接受帕妥珠单抗治疗，每周接受紫杉醇治疗12周。主要目标是评估残余癌症负荷（RCB）为0或I的患者比例。主要次要目标包括6周时的pCR率，安全性和肿瘤大小变化。还进行了产生假设的相关评估。结果30例可评估患者在患者和肿瘤特征方面保持良好平衡。实验组中RCB 0或I的患者比例更高（100％vs标准组中的62.5％，p = 0.0035）。在ER阳性子集中，实验组中的所有患者均达到RCB 0-I，而标准组中的所有患者均达到RCB 0-I（p = 0.0035）。两组之间的不良事件相似。结论在早期HER2阳性乳腺癌中，T-DM1，拉帕替尼和nab-紫杉醇的新辅助治疗比标准治疗更有效，特别是在ER阳性队列中。试验注册Clinicaltrials.gov NCT02073487，2014年2月27日。