829P - Tumour Vascular Endothelial Growth Factor (VEGF) and Vascular Endothelial Growth Factor Receptors (VEGFR) Polymorphisms and Clinical Outcome in Advanced Renal Cell Carcinoma Patients Receiving First Line Sunitinib

Abstract

ABSTRACT Background The introduction of novel treatments has radically changed the approach to the treatment of metastatic renal cell carcinoma (mRCC). Currently TKIs directed against the VEGF pathway are the therapeutic strongholds. However, criteria for treatment selection are largely lacking. In this study we assessed the role of VEGF and VEGFR polymorphisms, in the prediction of the clinical outcome in mRCC patients. Methods Forty-one formalin-fixed paraffin-embedded tissue blocks from mRCC patients receiving first-line sunitinib were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). SNPs results were correlated with progression free survival (PFS) and overall survival (OS). Results Forty-one patients with metastatic renal cell carcinoma were available for our analysis. All patients received sunitinib as fist-line treatment with standard schedule, dose reduction was applied in patients with grade 3 and 4 toxicities. Median PFS was of 8,22 months, while median OS was of 32,13 months. VEGF A rs833061 polymorphism resulted statistically significant in PFS (17 months for CC + CT vs 4 months for TT; p = 0,0001) and OS (36 months for CC + CT vs 8 months for TT; p = 0,0040). VEGF A rs699947 was statistically significant for PFS (17 months for AA + AC vs 4 months for CC; p = 0,0001) and OS (36 months for AA + AC vs 11 for CC; p = 0,0059). VEGF A rs2010963 was significant in PFS (17 months for GG vs 5 for GC vs 3 for CC; p = 0,0186). VEGR3 rs6877011 was significant in PFS (12 months for CC vs 4 for CG; p = 0,0221) and OS (36 months for CC vs 17 for CG; p = 0,0052). Conclusions in our analysis patients with TT polymorphism of rs833061, CC polymorphism rs699947 and CC polymorphism of rs2010963 seem to have a worse PFS and OS in first line. VEGF-A gene polimorphisms are probably connected with the control of the neoangiogenesis, maybe controlling vasculature normalization. Patients with CG polymorphism of rs6877011 seem equally to have a poor impact of first line therapy. VEGFR-3 seems to be involved in vessels sprouting and architecture. Disclosure All authors have declared no conflicts of interest.