Journal Article

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)

Belcheva, Anna, Boone, Toniva, Darcourt, Jorge G., Li, Xiaoxian, Niravath, Poly A., Kaklamani, Virginia G., Creamer, Sarah L., Qian, Wei, Meisel, Jane L., Kuhn, John G., Chang, Jenny C., Schwartz, Mary R., Ensor, Joe E., Zhao, Jing, Rosato, Roberto R., Patel, Tejal A., Rodriguez, Angel A.

2019

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adjuvant chemotherapy / Ado-trastuzumab emtansine / Ado-Trastuzumab Emtansine - administration & dosage / Ado-Trastuzumab Emtansine - adverse effects / Ado-Trastuzumab Emtansine - therapeutic use / Adult / Aged / Albumins - administration & dosage / Albumins - adverse effects / Albumins - therapeutic use / Analysis / Antineoplastic agents / Antineoplastic Combined Chemotherapy Protocols - administration & dosage / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Biomarkers, Tumor - analysis / Biomedical and Life Sciences / Biomedicine / Breast cancer / Breast Neoplasms - drug therapy / Breast Neoplasms - metabolism / Breast Neoplasms - pathology / Cancer metastasis / Cancer Research / Cancer therapies / Chemotherapy / Clinical trials / Comparative analysis / Consortia / Drug dosages / Drug therapy / Epidermal growth factor / Epidermal growth factors / ErbB-2 protein / Estrogen receptors / Estrogens / Female / HER2 / Humans / Immunotherapy / Inhibitor drugs / Labels / Lapatinib / Lapatinib - administration & dosage / Lapatinib - adverse effects / Lapatinib - therapeutic use / Medical prognosis / Menopause / Metastases / Metastasis / Middle Aged / Monoclonal antibodies / Nab-paclitaxel / Neoadjuvant / Neoadjuvant Therapy / NMR / Nuclear magnetic resonance / Oncology / Paclitaxel / Paclitaxel - administration & dosage / Paclitaxel - adverse effects / Paclitaxel - therapeutic use / Patients / Pertuzumab / Phenols (Class of compounds) / Receptor, ErbB-2 - antagonists & inhibitors / Receptor, ErbB-2 - metabolism / Research Article / Response rates / Surgical Oncology / T-DM1 / Targeted cancer therapy / Trastuzumab / Treatment Outcome / Tumor Burden - drug effects / Tumors