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Abstract Background: The addition of trastuzumab to neoadjuvant chemotherapy has significantly improved pathological complete response (pCR) in patients with HER2-positive early breast cancer (BC). Lapatinib, a dual HER2/EGFR tyrosine kinase inhibitor, combined with chemotherapy has significantly improved progression free survival in patients with metastatic HER2-positive BC. Additionally, lapatinib combined with trastuzumab improved disease-free and overall survival in patients with metastatic HER2-positive BC. The NeoALTTO trial is testing the efficacy of lapatinib, trastuzumab or their combination together with paclitaxel when given as neoadjuvant therapy in patients with HER2-positive BC. Material and Methods: NeoALTTO is an international, multicenter, randomized study comparing the efficacy of lapatinib plus paclitaxel, versus trastuzumab plus paclitaxel, versus concomitant lapatinib and trastuzumab plus paclitaxel given as neoadjuvant treatment in HER2- positive primary BC. From January, 2008, to December, 2009, 455 patients were randomized from 99 participating sites. Patients were randomized to receive either lapatinib 1500 mg/d (154 pts), or trastuzumab 4 mg/kg IV loading dose followed by 2 mg/kg IV weekly (149 pts), or lapatinib 1000 mg/d with trastuzumab for a total of 6 weeks (152 pts). After this biological window, patients continued on the same targeted therapy plus weekly paclitaxel 80 mg/m2 for a further 12 weeks, until definitive surgery (total neoadjuvant therapy duration of 18 weeks). After surgery, patients received 3 cycles of adjuvant FEC followed by the same targeted therapy as in the biological window of the neoadjuvant phase for a further 34 weeks (to complete 52 weeks of anti-HER2 therapy). The primary objective of the study is to evaluate and compare among the three arms the rate of pCR, defined as the absence of invasive cancer in the breast at the time of surgery. Secondary objectives include objective response rate, safety, pathologic node-negative status, rate of conversion to breast conservation, disease-free survival and overall survival. All patients underwent tumor biopsies for comparative pharmacodynamic analyses before beginning therapy and on day 15 of the biological therapy window. A subset of patients also participated in PET/CT and circulating tumor cells substudies. Results: The last breast surgery was performed in May 2010. Data cleaning and analysis will be complete by November 2010 and results for safety and the primary objective (pCR) of this important phase III trial will be presented at the meeting. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S3-3.
Baselga et al. (Wed,) studied this question.