Effect of serum HER2, TIMP-1, and CAIX on outcome in HER2+ metastatic breast cancer patients treated in first line with lapatinib or trastuzumab combined with taxane: NCIC CTG MA.31.

617 Background: The lapatinib-taxane combination led to shorter PFS than trastuzumab-taxane in HER2+ metastatic breast cancer. We investigated the prognostic and predictive effects of pretreatment serum HER2, CA IX, and TIMP-1. Methods: MA.31 accrued 652 patients; 537 (82%) were centrally-confirmed HER2+. Biomarkers were categorized for univariate and multivariate predictive investigations with a median cut-point, ULN cut-points (15 ng/ml for HER2; 506 pg/ml for CAIX; 454 pg/ml for TIMP-1), and custom cut-points (30 and 100 ng/ml for HER2). Stratified step-wise forward Cox multivariate analysis used continuous and categorical biomarkers for PFS in the ITT and central HER2+ populations; central HER2+ biomarker results are shown. Results: Serum was banked for 472 (72%) of 652 patients. Higher serum HER2 (>median; >15; >30; or >100 ng/ml; p=0.05-0.002); higher CAIX (>median; >506 pg/ml; p=0.02; p=0.001); and higher TIMP-1 (>median; >454 pg/ml; p=0.001; p=0.02) had worse univariate PFS. In multivariate analys...