A randomized, controlled phase II trial of neoadjuvant ado-trastuzumab emtansine, lapatinib, and nab-paclitaxel versus trastuzumab, pertuzumab, and paclitaxel in HER2-positive breast cancer (TEAL study)

被引:49
作者
Patel, Tejal A. [1 ,2 ]
Ensor, Joe E. [1 ,2 ]
Creamer, Sarah L. [1 ]
Boone, Toniva [1 ]
Rodriguez, Angel A. [1 ,2 ]
Niravath, Poly A. [1 ,2 ]
Darcourt, Jorge G. [1 ,2 ]
Meisel, Jane L. [4 ]
Li, Xiaoxian [4 ]
Zhao, Jing [5 ]
Kuhn, John G. [3 ]
Rosato, Roberto R. [2 ]
Qian, Wei [2 ]
Belcheva, Anna [1 ]
Schwartz, Mary R. [6 ]
Kaklamani, Virginia G. [3 ]
Chang, Jenny C. [1 ,2 ,7 ]
机构
[1] Houston Methodist Canc Ctr, 6445 S Main St, Houston, TX 77030 USA
[2] Houston Methodist Res Inst, 6670 Bertner Ave, Houston, TX 77030 USA
[3] Univ Texas Hlth Sci Ctr San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA
[4] Emory Univ, Sch Med, Winship Canc Inst, 1365 Clifton Rd, Atlanta, GA 30322 USA
[5] Qingdao Univ, Affiliated Hosp, 16 Jiangsu Rd, Qingdao Shi, Shandong Sheng, Peoples R China
[6] Houston Methodist Hosp, Dept Pathol & Genom Med, 6565 Fannin St, Houston, TX 77030 USA
[7] Weill Cornell Med, 1300 York Ave, New York, NY 10065 USA
关键词
Neoadjuvant; HER2; Ado-trastuzumab emtansine; T-DM1; Lapatinib; Nab-paclitaxel; RCB; PLUS DOCETAXEL; OPEN-LABEL; MULTICENTER; EFFICACY; CHEMOTHERAPY; SAFETY;
D O I
10.1186/s13058-019-1186-0
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页数:9
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