VEGF single nucleotide polymorphisms (SNPs) and correlation to sunitinib-induced hypertension (HTN) in metastatic renal cell carcinoma (mRCC) patients (pts)

Abstract

5005 Background: VEGF SNPs (-634 C/C and -1498 T/T) have been associated with protection from grade III/IV HTN in breast cancer pts receiving bevacizumab plus paclitaxel (J Clin Oncol. 26:4672–4678). The aim of this study was to retrospectively evaluate the association among VEGF SNPs and the development of HTN in mRCC pts receiving sunitinib. Methods: mRCC patients receiving sunitinib (50mg 4/2) with available blood pressure (BP) data and germline DNA were retrospectively identified. All BP measurements were recorded in clinic approximately every 4 weeks. Genomic DNA was isolated from peripheral blood lymphocytes. VEGF SNP's -634 C/G (5’UTR polymorphism, NCBI reference sequence #2010963), and -1498 C/T (promoter polymorphism NCBI reference sequence #833061) were amplified using primers designed to flanking sequences for the respective SNPs. Genotypes were assigned following sequence analysis. Data were analyzed using parametric and non-parametric methods. Results: Sixty-four patients were identified of which 63 had available SNP data; 78% were male; median age was 60 (range 35–80); 67% ECOG performance status of 0; 89% prior nephrectomy and 63% previously treated with cytokines (48%) and/or a TKI (24%). Median systolic and diastolic BPs at baseline were 139 mmHg (range, 93–190) and 80 mmHg (range, 47–103), respectively; 57% of patients were being treated with anti-hypertensive therapies at baseline. The distribution of pts for the VEGF-634 genotype was C/C (10%), C/G (33%) and G/G (57%). VEGF-634 C/C < C/G < G/G genotypes were associated with increasing frequency and duration of HTN (diastolic > 90 mmHg and/or systolic > 150 mmHg) during treatment with sunitinib (p = 0.03 and p = 0.007, respectively) and remained significant adjusting for baseline BP and use of anti-HTN meds (p = 0.05 and 0.02, respectively). Similar correlations were not found for VEGF-1498 genotypes. There was no association between VEGF SNPs and tumor volume reduction or PFS. Conclusions: VEGF SNP-634 G/G genotype is correlated with HTN during treatment with sunitinib in mRCC pts. [Table: see text]