The predictive value of single nucleotide polymorphisms in the VEGF system to the efficacy of first-line treatment with bevacizumab plus chemotherapy in patients with metastatic colorectal cancer: results from the Nordic ACT trial

Abstract

Purpose: Bevacizumab and chemotherapy is a common choice for first-line treatment of metastatic colorectal cancer (mCRC). So far, no predictive markers have been identified. The aim was to investigate the possible predictive value of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) system in this setting.

Methods: Pre-treatment blood samples and response evaluations were available from 218 of the 249 included patients. All patients received bevacizumab and chemotherapy comprising fluorouracil and leucovorin or capecitabine combined with either oxaliplatin (FOLFOX or XELOX, n = 183) or irinotecan (FOLFIRI or XELIRI, n = 66). Germline DNA was isolated from whole blood, and five SNPs in the VEGF-A gene, one SNP in the VEGF receptor 1 (VEGFR-1) gene and three SNPs in the VEGFR-2 gene were analysed by polymerase chain reaction. Response was evaluated according to RECIST version 1.0, and the association to genotypes was analysed using Fisher's exact test.

Results: The VEGFR-1 319 C/A SNP was significantly associated with response. Objective response was observed in 36% of the patients with CC genotype, 40% with CA and 56% with AA, p = 0.048. The response rates also differed significantly between patients with C-allele containing genotypes (CC + CA) (39%) and patients homozygous for the A-allele (AA) (56%), p = 0.015. There was no correlation between response rates and the remaining SNPs.

Conclusions: The VEGFR-1 319 C/A SNP is a potential predictive marker for bevacizumab plus chemotherapy in patients with mCRC. Patients with the A allele appeared to have increased response rates. The results call for validation.