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)

• Type of Material: Article
• Authors: Tejal A. Patel, Houston Methodist Cancer Center; Joe E. Ensor, Houston Methodist Cancer Center; Sarah L. Creamer, Houston Methodist Cancer Center; Toniva Boone, Houston Methodist Cancer Center; Angel A. Rodriguez, Houston Methodist Cancer Center; Poly A. Niravath, Houston Methodist Cancer Center; Jorge G. Darcourt, Houston Methodist Cancer Center; Jane L. Meisel, Emory University; Xiaoxian Li, Emory University; Jing Zhao, Qingdao University; John G. Kuhn, University of Texas Health Science Center at San Antonio; Roberto R. Rosato, Houston Methodist Research Institute; Wei Qian, Houston Methodist Research Institute; Anna Belcheva, Houston Methodist Cancer Center; Mary R. Schwartz, Houston Methodist Hospital; Virginia G. Kaklamani, University of Texas Health Science Center at San Antonio; Jenny C. Chang, Houston Methodist Cancer Center
• Language: English
• Date: 2019-09-02
• Publisher: BMC (part of Springer Nature)
• Publication Version: Final Published Version
• Copyright Statement: © 2019 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13058-019-1186-0
• Title of Journal or Parent Work: Breast Cancer Research
• ISSN: 1465-5411
• Volume: 21
• Issue: 1
• Start Page: 100
• End Page: 100
• Grant/Funding Information: Both Celgene and Novartis reviewed the manuscript before publication; neither company was involved with the implementation of the protocol, analysis of the data, or preparation of the manuscript.; For this trial, nab-paclitaxel and lapatinib were provided by Celgene and Novartis, respectively.; T-DM1 was provided by both Celgene and Novartis.
• Keywords: Science & Technology; Ado-trastuzumab emtansine; RCB; EFFICACY; Lapatinib; Nab-paclitaxel; OPEN-LABEL; Life Sciences & Biomedicine; CHEMOTHERAPY; Oncology; HER2; MULTICENTER; T-DM1; Neoadjuvant; PLUS DOCETAXEL; SAFETY
• Research Categories: Health Sciences, Oncology

Abstract

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.