The purpose of this study is to evaluate the efficacy and safety of weekly paclitaxel and carboplatin, in combination with lapatinib, in the neoadjuvant treatment of non-metastatic erbB2-positive breast cancer. Secondary objectives include: * To determine the safety and tolerability of weekly paclitaxel and carboplatin, combined with lapatinib, in an Asian population * To determine breast conservation rates following neoadjuvant paclitaxel/ carboplatin/ lapatinib * To determine clinical response rates and relapse-free survival of patients treated with neoadjuvant paclitaxel/ carboplatin/ lapatinib * To identify predictive tumour biomarkers for pathologic complete response The investigators hypothesize that pathologic complete response rates will be improved from 15% to 35% with the neoadjuvant regimen of carboplatin/ paclitaxel/ lapatinib compared to standard chemotherapy alone in HER2 positive early stage breast cancers.
* Pathologic complete response following neoadjuvant chemotherapy has been shown to be an independent, strong predictor of disease-free and overall survival in operable breast cancer * The addition of neoadjuvant trastuzumab to chemotherapy results in a 2-3 fold increase in pCR rates in operable ErbB2-positive breast cancer * Lapatinib is being explored as an alternative to trastuzumab in large clinical trials in operable ErbB2-positive breast cancer * In a randomised phase III adjuvant trial, BCIRG 006, non-anthracycline chemotherapy (docetaxel and carboplatin) has been shown to be as effective as conventional sequential anthracycline-containing chemotherapy and docetaxel, in combination with trastuzumab, but with improved cardiac safety * Weekly paclitaxel has been shown in a randomized phase III study to be the optimal adjuvant taxane regimen * Weekly paclitaxel and carboplatin, in combination with lapatinib, has demonstrated safety and efficacy in Phase I/II clinical studies of metastatic breast and ovarian cancer * The investigators aim to assess the efficacy of a non-anthracycline containing regimen, weekly paclitaxel and carboplatin, in combination with lapatinib in inducing pCR in the neoadjuvant treatment of ErbB2-positive non-metastatic breast cancer. The investigators hypothesize that this combination will achieve pCR rates of at least 35%
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
34
Drug doses for the neoadjuvant regimen: * Paclitaxel 80mg/m2, day 1, 8, 15 of a 21-day cycle * Carboplatin AUC of 2, day 1, 8 of a 21-day cycle * Lapatinib 750mg daily continuously
National University Hospital
Singapore, Singapore
Rate of pathologic complete response
Time frame: 12 weeks
Treatment related toxicities
Time frame: 12 weeks
Breast conservation rates
Time frame: 16 weeks
Clinical response rates
Time frame: 1 year
Relapse free survival (RFS)
Time frame: 2 years
Identification of tumor biomarkers that predict pathologic complete response
Time frame: 16 weeks
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