Predictive and prognostic impact of plasma vascular endothelial growth factor levels in non-small-cell lung cancer patients treated with gefitinib

Abstract

13030 Background: In non-small cell lung cancer (NSCLC), sensitivity to gefitinib is associated with activating mutations of the epidermal growth factor receptor (EGFR). Tumor samples obtained for diagnosis of NSCLC are limited and often unsuitable for analysis of mutations. Other biomarkers are thus needed. We previously reported that serum vascular endothelial growth factor (VEGF) levels were significantly lower in responders to gefitinib than non-responders. To assess levels of circulating VEGF as a predictive and prognostic marker of gefitinib treatment in NSCLC patients, we examined the associations between plasma VEGF levels before gefitinib treatment and clinical outcome. Methods: Eighty four NSCLC patients treated with gefitinib were enrolled into this investigation. Plasma VEGF levels were measured in blood samples before gefitinib administration. Patients were grouped according to VEGF level around a cut-off of 80.7 pg/ml, based on results from normal controls. Response to gefitinib was judged using RECIST guidelines. Time to progression (TTP) and overall survival (OS) following gefitinib treatment were calculated using Kaplan-Meier methods. Groups were compared using log-rank test. We evaluated the immunohistochemical expression of VEGF and EGFR mutations in tumor samples from 37 patients. Results: Response rate was significantly higher with low VEGF level than with high VEGF level (p = 0.0010). Multivariate analysis for response to gefitinib including sex, histology, smoking status, performance status and plasma VEGF level identified only low VEGF level as predictive of response to gefitinib. Low VEGF level was also correlated with prolonged median TTP (4.1 months vs. 1.1 months, p = 0.0081) and OS (11.1 months vs. 5.4 months, p = 0.0290). Multivariate analysis for survival revealed low VEGF level as associated with prolonged TTP (p = 0.0081) and OS (p = 0.0708). Plasma VEGF level was not associated with either VEGF expression or EGFR mutations of tumor tissue. Conclusions: Our results suggest that plasma VEGF levels before gefitinib treatment are predictive of response to gefitinib and prognostic of patients who receive gefitinib. [Table: see text]