Determining relevant biomarkers from tissue and serum that may predict response to single agent lapatinib in trastuzumab refractory metastatic breast cancer

Abstract

3004 Background: Lapatinib is an oral tyrosine kinase inhibitor that potently inhibits both ErbB1 and ErbB2 tyrosine kinase activity. Results of two Phase II trials in metastatic breast cancer (MBC) suggest activity of lapatinib in trastuzumab (T) pretreated patients. The main objective of this report was a combined biomarker analysis from these two large studies to evaluate correlations between clinical parameters, tissue/serum biomarker expression and response to lapatinib. Methods: Eligible patients had MBC with disease progression following T-containing regimens in the 1st phase II study and were anthracycline, taxane, capecitabine and T exposed in the 2nd phase II study. Tumor tissues were obtained on each patient from the time of most recent biopsy. Using standard IHC techniques, tumors were stained for: ErbB1-4, IGF1R, truncated ErbB2 (p95), heregulin and p-Erk 1/2. Sequential quanitation of extra-cellular domain (ECD) for both ErbB1 and ErbB2 were obtained. Results: Investigator reported efficacy ...