A randomized, multicentre, open-label, Phase II study of the efficacy and safety of lapatinib plus epirubicin and cyclophosphamide (EC90-L) followed by weekly paclitaxel and lapatinib (PX-L) compared with EC90 followed by weekly paclitaxel and trastuzumab (PX-T), as neoadjuvant therapy in patients with previously untreated ErbB2-overexpressing Stage I - IIIA invasive breast cancer with primary tumour size > 1cm

INTERVENTION: Trade Name: Tyverb Product Name: Lapatinib Product Code: GW572016 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: Lapatinib CAS Number: 388082‐78‐8 Current Sponsor code: GW572016 Other descriptive name: ditosylate monohydrate Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 250‐ Trade Name: Herceptin Product Name: Trastuzumab Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: Trastuzumab CAS Number: 18022‐69‐1 Concentration unit: mg/kg milligram(s)/kilogram Concentration type: equal Concentration number: 150 ‐ CONDITION: patients with previously untreated ErbB2‐overexpressing Stage I ‐ IIIA invasive breast cancer with primary tumour size > 1cm. ; MedDRA version: 12.1 Level: LLT Classification code 10006187 Term: Breast cancer PRIMARY OUTCOME: Main Objective: The primary objective of the study is to compare the rate of pathologic complete response (pCR) in the breast at the time of definitive surgery. Primary end point(s): The primary efficacy endpoint of this study is pathologic complete response (pCR) in the breast at the time of definitive surgery defined as the absence of invasive disease. Secondary Objective: • The pCR rate in the breast and axilla at the time of definitive surgery in the; study treatment regimen versus the reference regimen.; ; • Overall response rate (complete plus partial response) in the breast and axilla.; ; • The breast conservation rate. INCLUSION CRITERIA: 1. Signed written informed consent approved by an Independent Ethics Committee (IEC) and obtained prior to any study specific screening procedures. 2. Female patients aged =18 years. 3. Eastern Cooperative Oncology Group (ECOG) performance status 0 –1. 4. Histologically confirmed, previously untreated, operable Stage I‐IIIA invasive breast cancer: • Primary tumour greater than 1 cm in diameter measured by clinical examination and confirmed by at least one imaging study (mammography, breast ultrasound or MRI). • In the case of a multifocal tumour (defined as the presence of two or more foci of cancer within the same breast quadrant), the largest lesion must be >1 cm and is designated as the “target” lesion for all subsequent tumour evaluations. 5. Over expression and/or amplification of ErbB2 in the invasive component of the primary tumour according to one of the following definitions. Central laboratory confirmation is not