Identification of a 6 gene molecular predictor of lapatinib related benefit: From breast cancer cell lines to a phase III trial

Abstract

1043 Background: Identification of molecular predictors of response is an important aspect of efforts to individualize cancer treatment. Responses to lapatinib (L), an oral, dual inhibitor of HER2 and EGFR approved in combination with capecitabine for HER2+ metastatic breast cancer (MBC), were evaluated in a panel of BC cell lines. Computational approaches were then used to identify a 6-gene predictor of quantitative response to L. Methods: The clinical utility of the 6-gene predictor was tested retrospectively using a Panomics assay in tumor tissue samples from HER2-negative or HER2-untested MBC patients (pts) enrolled in a phase III trial of paclitaxel (P) or P+L. Panomics results were compared with HER2 fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) status and discordant cases were analyzed. Dichotomous response patterns of HER2+ pts and a computational model that predicts L sensitivity or resistance is described. Results: Tissue samples from 302 pts were tested using the bran...