Abstract
BackgroundNeoadjuvant 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.MethodsStratification 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.ResultsThe 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.ConclusionIn 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 registrationClinicaltrials.gov NCT02073487, February 27, 2014.
Highlights
Neoadjuvant dual human epidermal growth factor receptor (HER2) blockade with trastuzumab and pertuzumab plus paclitaxel leads to an overall pathologic complete response rate of 46%
In early-stage Human epidermal growth factor receptor (HER2)-positive breast cancer, the neoadjuvant treatment with Ado-trastuzumab emtansine (T-DM1), lapatinib, and nab-paclitaxel was more effective than the standard treatment, in the estrogen receptor (ER)-positive cohort
Fourteen patients were randomly assigned to the experimental arm (T-DM1 + lapatinib + nab-paclitaxel) and 16 to the standard arm
Summary
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. In the NeoALTTO study, dual HER2 blockade with lapatinib and trastuzumab plus paclitaxel resulted in a higher pCR rate when compared with trastuzumab/paclitaxel (51.3% vs 29.5%) [3]. In the NeoSphere study, dual blockade with pertuzumab and trastuzumab plus docetaxel compared to trastuzumab/docetaxel had a significantly improved pCR rate (46% vs 29%) [4]. The combination of trastuzumab, pertuzumab, and paclitaxel was utilized as the comparator neoadjuvant standard treatment
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