Randomized Phase Ii Trial Of Capecitabine And Lapatinib With Or Without Cixutumumab In Patients With Her2+Breast Cancer Previously Treated With Trastuzumab And An Anthracycline And/Or A Taxane: Ncctg N0733 (Alliance).

632 Background: Crosstalk between the insulin-like growth factor (IGF) and HER2 pathways in multiple preclinical models suggest a mechanism of resistance to HER2-targeted therapy. Cixutumumab (CIX, IMC-A12), an anti-IGF-1 Receptor monoclonal antibody, was investigated in combination with capecitabine and lapatinib (cape/lap) to determine if the addition of an IGF target agent would improve PFS compared to cape/lap in unselected HER2+ metastatic breast cancer (mbc) patients (pts). IGF binding protein (IGFBP) levels may be important in predicting tumor dependence on IGF signaling and are potential biomarkers. Methods: Following an initial safety cohort, this open label phase II study randomized (2:1) pts to cape/lap with CIX (Arm B) or cape/lap (Arm A). Primary endpoint was progression-free survival (PFS) with 144 pts planned for a target hazard ratio of 0.56. PFS was estimated using Kaplan-Meier and compared using Cox regression. Secondary endpoints included assessing the overall survival and treatment tol...