BackgroundCapecitabine (C) administered for 14 days followed by a 7 day rest (14—7) in combination with lapatinib (L) improved TTP in patients with HER2(+) metastatic breast cancer (MBC) that progressed following trastuzumab (T). We applied mathematical methods to C dosing which predicted 7 days of treatment (Tx) followed by 7 days of rest (7—7) to be optimal. In animal models, C(7—7) was better tolerated than C(14—7) at higher doses and led to improved survival. A phase I study in patients (pts) with MBC concluded the MTD of C(7—7) is 2,000mg BID. To optimize the combination of C+L, we are testing C(7—7) + L.MethodsEligible pts have measurable, HER2(+) MBC with progression following trastuzumab. HER2(+)=3+ or FISH-amplified. Pts have normal LVEF by MUGA, ECOG performance status (PS) ≤2 and normal organ function. Prior therapy is limited to 6 months and PFS. Using a Simon optimal 2-stage design, with alpha 10% and power 90% to discriminate between RR 10% and 25%, 21 pts will be accrued to the 1st stage. If >2 patients respond, 29 additional pts will be enrolled. If >7/40 pts respond, then C(7—7) + L will be considered worthy of further study.ResultsAs of 5/28/09, 12 pts are enrolled; 6 are evaluable for response. Median (med) age 61 years (41-71), med ECOG PS 0 (0-2), ER/PR(+) 5, HER2(+) 12. Sites of MBC: Viscera 5, Brain 2. Med LVEF 64% (51-71%). Prior Tx: Adjuvant: CRx (7), hormone Tx (3), T (4); MBC: CRx (6), hormone Tx (4), T (8). After a med of 3 cycles (1-8), 6 pts are evaluable for response: CR 0, PR 1, SD>6mo 2, SD 10% of pts includes: hand-foot syndrome (Gr 3: 8%, Gr 2: 17%) and diarrhea (Gr 2: 17%). There were no declines in LVEF.ConclusionCapecitabine (7—7) plus lapatinib appears well-tolerated and demonstrates activity in pts with HER2(+) MBC that has progressed following trastuzumab based therapy. Additional efficacy and safety data is expected prior to this meeting. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5113.