Neo ALTTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) Study

This was a parallel group, three-arm, randomized, multicenter, open-label phase III study. The study compared the efficacy and tolerability of neoadjuvant lapatinib and paclitaxel, versus trastuzumab and paclitaxel, versus the combination of lapatinib with trastuzumab and paclitaxel given as neoadjuvant treatment in HER2/ErbB2 over-expressing and/or amplified primary breast cancer. Subjects were randomized to receive lapatinib, trastuzumab or lapatinib plus trastuzumab for a total of 6 weeks. After this biological window, subjects continued on the same targeted therapy plus weekly paclitaxel for a further 12 weeks, until definitive surgery (total neoadjuvant therapy duration of 18 weeks). Paclitaxel could be initiated at Week 4 if there is evidence of progressive disease (PD) at that time. Within 6 weeks after surgery, subjects received 3 cycles of adjuvant 5-flourouracil, epirubicin and cyclophosphamide (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). After completing 52 weeks of (neo-)/adjuvant anti-HER2 therapy, subjects were scheduled to attend post-treatment follow-up every 3 months during the first year (months 12, 15, 18, 21, and 24), every 6months in Years 3 to 5 inclusive, and annually thereafter up to Year 10. Each subject was to be followed for 10 Years. All subjects were to be followed for EFS and OS up to 10 years from last subject randomized.