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
Authors: Gajria D , Theodoulou M , Feigin K , Patil S , Geneus S , Drullinsky P , D'Andrea G , Lake D , Norton L , Hudis C , Traina TA. 
Published: April 2011

Abstract
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 &lt;3 chemotherapy regimens (CRx) for MBC (no prior fluoropyrimidine). Therapy was C (2,000 mg orally twice daily, 7—7) with L (1,250 mg orally daily); cycle length was 4 weeks. Pts were evaluated for toxicity every 4 weeks and for LVEF by MUGA every 12 weeks. Response was assessed every 12 weeks. Primary endpoint was response rate (RR). Secondary endpoints included toxicity by NCI CTCv3, stable disease (SD) &gt; 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 &gt;2 pts responded, then 29 additional pts were to have been enrolled to 2nd stage. If &gt;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 &gt;6 months, 9 SD &lt;6 months. Med PFS is 36 weeks (95% CI 23-not reached). Four pts are too early for response assessment. Nine pts remain on treatment. One pt experienced grade (gr) 4 treatment-related anemia and had refused supportive erythropoietin. Treatment-related gr 2 or 3 toxicities in &gt;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.