Abstract
Abstract Purpose: It has been suggested that hepatocyte growth factor (HGF) and insulin-like growth factor binding protein (IGFBP)-3 are associated with gefitinib resistance in non-small cell lung cancer (NSCLC). We investigated the predictive and prognostic roles of these proteins in NSCLC patients treated with gefitinib. Methods: Of 106 patients enrolled in the randomized phase II study of gefitinib, 97 had plasma samples available for ELISA testing. Of these samples, seven and eight, respectively, had HGF and IGFBP-3 values that could not be measured. Therefore, the correlations between clinical outcomes and plasma levels of HGF and IGFBP-3 were evaluated in 90 and 89 patients, respectively. Results: Plasma HGF levels were significantly higher in older patients, male patients, patients with squamous cell carcinoma, current smokers, and patients with EGFR wild-type tumors. Low HGF levels were significantly associated with higher response rate (RR), and longer progression-free survival (PFS) and overall survival (OS) irrespective of EGFR mutation status. In a multivariate analysis, the presence of EGFR mutations (HR, 0.42; 95% CI, 0.24 to 0.73; P=0.002) and low HGF levels (HR, 0.58; 95% CI, 0.35 to 0.95; P=0.031) were independently predictive of longer PFS, and an ECOG PS of 0 (HR, 2.95; 95% CI, 1.57-5.54; P=0.001) and low HGF levels (HR, 0.40; 95% CI, 0.22-0.72; P=0.002) were independently predictive of longer OS. No statistically significant differences were found for IGFBP-3. Conclusion: High HGF levels are significantly associated with resistance to gefitinib and can be used as a predictive marker for the differential outcome of gefitinib treatment in NSCLC irrespective of EGFR mutation status. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4119. doi:10.1158/1538-7445.AM2011-4119
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