Data from FGFR1 Expression Levels Predict BGJ398 Sensitivity of FGFR1-Dependent Head and Neck Squamous Cell Cancers

Abstract

<div>Abstract<p><b>Purpose:</b> <i>FGFR1</i> copy-number gain (CNG) occurs in head and neck squamous cell cancers (HNSCC) and is used for patient selection in FGFR-specific inhibitor clinical trials. This study explores FGFR1 mRNA and protein levels in HNSCC cell lines, primary tumors, and patient-derived xenografts (PDX) as predictors of sensitivity to the FGFR inhibitor, NVP-BGJ398.</p><p><b>Experimental Design:</b> <i>FGFR1</i> status, expression levels, and BGJ398 sensitive growth were measured in 12 HNSCC cell lines. Primary HNSCCs (<i>n</i> = 353) were assessed for <i>FGFR1</i> CNG and mRNA levels, and HNSCC TCGA data were interrogated as an independent sample set. HNSCC PDXs (<i>n</i> = 39) were submitted to <i>FGFR1</i> copy-number detection and mRNA assays to identify putative FGFR1-dependent tumors.</p><p><b>Results:</b> Cell line sensitivity to BGJ398 is associated with FGFR1 mRNA and protein levels, not <i>FGFR1</i> CNG. Thirty-one percent of primary HNSCC tumors expressed FGFR1 mRNA, 18% exhibited <i>FGFR1</i> CNG, 35% of amplified tumors were also positive for FGFR1 mRNA. This relationship was confirmed with the TCGA dataset. Using high FGFR1 mRNA for selection, 2 HNSCC PDXs were identified, one of which also exhibited <i>FGFR1</i> CNG. The nonamplified tumor with high mRNA levels exhibited <i>in vivo</i> sensitivity to BGJ398.</p><p><b>Conclusions:</b> FGFR1 expression associates with BGJ398 sensitivity in HNSCC cell lines and predicts tyrosine kinase inhibitor sensitivity in PDXs. Our results support FGFR1 mRNA or protein expression, rather than <i>FGFR1</i> CNG as a predictive biomarker for the response to FGFR inhibitors in a subset of patients suffering from HNSCC. <i>Clin Cancer Res; 21(19); 4356–64. ©2015 AACR</i>.</p></div>