Abstract Abstract #2109 Background: Despite the impressive results of the recently released trastuzumab adjuvant therapy trials, 15% of patients with HER2 overexpressing or amplified breast cancer developed tumor relapse at 4 years. Lapatinib is a small molecule reversible TKI that inhibits both ErbB1 and ErbB2. The current study was developed to assess the cardiac safety and feasibility of adding lapatinib to paclitaxel and trastuzumab following as part of adjuvant therapy.
 Methods: A single-arm phase II study of doxorubicin (A, 60 mg/m2 day 1) and cyclophosphamide (C, 600 mg/m2 day 1) [q2w or q3w for 4 cycles]; followed by paclitaxel (P, 80 mg/m2 days 1, 8, 15), trastuzumab (T, 4 mg/kg loading dose then 2 mg/kg days 1, 8, 15), and lapatinib (L, 1000 mg days 1-21) [12 weeks]; followed by T (6 mg/kg day 1) and L (1000 mg days 1-21) [40 weeks] was conducted. The primary endpoint was the incidence of congestive heart failure. The current unplanned safety analysis was undertaken due to the observance of a high rate of G3/4 diarrhea.
 Results: From April 2007 to June 2008, 98 pts were enrolled and initiated study treatment. Median age was 51 (range 32-72). Among 83 pts with adverse event (AE) data available, 50 (60%) pts have experienced a G3/4 non-hematologic AE. During post-AC treatment, among 53 pts with AE data available, 31 (58.5%) patients have experienced a G3/4 non-hematologic AE with 24 (45%) patients reporting G3/4 diarrhea. Median cycle of onset of G3/4 diarrhea was cycle 5 (first cycle of PTL) with 16 (64%) cases first reported during cycle 5 and 5 (20%) cases first reported during cycle 6. Among 57, 46, 38, and 32 pts receiving treatment with PTL during cycles 5-8, 65%, 57%, 61%, and 72% of patients received the full L dose, respectively. 31 patients have ended active treatment with 10 due to patient refusal and 8 due to adverse events.
 Conclusions: Preliminary data suggest that L given concurrently with P and T at a dose of 1000 mg per day induces an unacceptable rate of moderate to severe diarrhea. Careful monitoring of diarrhea as well as L dose reduction and initiation of loperamide at first occurrence of diarrhea are recommended. The dose of L when given concurrently with P and T has been amended to 750 mg per day in the current study and safety data for the 1000 mg and 750 mg per day cohorts will be presented. Implications for the ongoing ALTTO study will also be presented. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2109.