Frequency of insulin-like growth factor 1 (IGFR-1) expression and correlation with clinical and selected molecular parameters in advanced non-small cell lung cancer (NSCLC) patients (pts)

Abstract

22080 Background: The epidermal growth factor receptor (EGFR) signaling pathway has become an important target in lung cancer with the success of EGFR tyrosine kinase inhibitors (TKI). The IGFR-1 signaling pathway has also been implicated in oncogenesis and cancer cell survival. The aim of the study was to determine the correlation of IGFR-1 expression with both clinical features of previously treated advanced NSCLC pts and molecular markers in the EGFR pathways in pts treated with gefitinib. Methods: Consecutive Expanded Access Trial pts with >1 week gefitinib were included for analysis. 83 pts had tissue evaluated for IGFR-1 immunohistochemistry (IHC). IGFR-1 positivity was defined as presence of any staining. 81 patients were evaluated for EGFR protein expression by IHC; EGFR gene copy number, and chromosome 7 copy number (c7) by fluorescence in situ hybridization (FISH), FISH positivity as defined by Cappuzzo et al, JNCI, 2005. Results: 78 pts had tissue with both IGFR-1 expression and FISH analyses available: median age 66, 36(46.2%) men, 48(61.5%) with adenocarcinoma, 12(15.4%) never smokers, and 71(91.0%) with performance status(PS) of 0. The response rate (including CR and PR) to gefitinib was 15.38%. Median progression free survival was 3.0 months. Median overall survival was 7.3 months. Positive IGFR-1 score (> 0) was seen in 71.08% of tissue samples. Positive IGFR-1 was marginally associated with smoking (p<0.1). No significant association was found between IGFR-1 score and age, gender, histology, or PS. There was a significant association between IGFR-1 positivity and the following parameters: EGFR IHC (p=0.002), c7 (p=0.03), and EGFR gene amplification (p-0.01). Conclusions: IGFR-1 expression is relatively frequent in NSCLC. In this group of NSCLC pts, IGFR expression by IHC did not correlate with clinical parameters. The significant correlations between IGFR expression by IHC and increased EGFR protein expression, EGFR gene amplification and c7 polysomy, suggest that combining an IGFR inhibitor with an EGFR TKI might improve outcomes in selected NSCLC pts. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca AstraZeneca