Abstract P6-11-12: A Novel Capecitabine Schedule (7 on — 7 off) Is Feasible with Lapatinib for Patients with HER2-Positive Metastatic Breast Cancer Refractory to Trastuzumab

Background Capecitabine (C) administered for 14 days followed by a 7 day rest (14—7) in combination with lapatinib (L) improved TTP in patients (pts) with HER2(+) metastatic breast cancer (MBC) that progressed following trastuzumab (T). Our mathematical modeling of C dosing predicted 7 days of therapy followed by 7 days of rest (7—7) to maximize efficacy and minimize drug-related toxicity. In xenograph models, C (7—7) was better tolerated than C (14—7) at higher doses and led to improved survival. We established the maximum tolerated dose of C (7—7) to be 2,000 mg twice daily and have studied C (7—7) in combination with targeted therapies. We now report the results of C (7—7) with L in pts with trastuzumab-refractory HER2(+) MBC. Methods Eligible pts had measurable, HER2(+) MBC with progression following T. HER2(+) is defined as 3+ on IHC or FISH-amplified. Pts had normal LVEF by MUGA, ECOG performance status (PS) ≥2, and 6 months, and progression free survival (PFS). Using a Simon optimal 2-stage design, with alpha 10% and power 90% to discriminate between RR 10% and 25%, 21 pts were planned for the 1st stage. If >2 pts responded, then 29 additional pts were to have been enrolled to 2nd stage. If >7/50 pts responded, C (7—7) with L would be considered worthy of further study. Results As of 6/14/10, 22 pts were enrolled on study with the following characteristics: median (med) age 55 years (42-72), med PS 0 (0-2), ER/PR(+) 12, HER2(+) 22, med LVEF 64% (51-70%). Sites of MBC include viscera 16, brain 3. Prior therapy includes 8 pts with adjuvant anthracycline and taxane exposure, 4 pts with adjuvant T, 18 pts with metastatic T, and a med of 1 CRx for MBC. After a med of 5 cycles (1-16), 18 patients are evaluable for response: 0 CR, 3 PR, 6 SD >6 months, 9 SD 10% of patients include: hand-foot syndrome (gr 3: 5%, gr2: 41%), diarrhea (gr 3: 0%, gr 2: 23%), elevated AST/ALT or bilirubin (gr 3: 0%, gr 2: 18%). There have been no declines in LVEF. Conclusion Due to slower than expected accrual and an anticipated randomized, phase III trial comparing C (7—7) with C (14—7), we closed this study to further accrual. However, our data suggests that C (7—7) with lapatinib is active, well-tolerated, feasible and associated with mild gastrointestinal toxicity in pts with trastuzumab-refractory, HER2(+) MBC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-11-12.