Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients

Sci Rep. 2016 Apr 27:6:25195. doi: 10.1038/srep25195.

Abstract

Regorafenib monotherapy is a potential option for metastatic colorectal cancer patients. However, the lack of predictive factors and the severe toxicities related to treatment have made its use in clinical practice challenging. Polymorphisms of VEGF and its receptor (VEGFR) genes might regulate angiogenesis and thus potentially influence outcome during anti-angiogenesis treatment such as regorafenib. Aim of our study was to evaluate the role of VEGF and VEGFR genotyping in determining clinical outcome for colorectal cancer patients receiving regorafenib. We retrospectively collected clinical data and samples (tumour or blood) of 138 metastatic colorectal cancer patients treated with regorafenib. We analysed the correlation of different VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs) with patients' progression-free survival (PFS) and overall survival (OS). Results from angiogenesis genotyping showed that only VEGF-A rs2010963 maintained an independent correlation with PFS and OS. Among clinical factors only ECOG PS was independently correlated with OS, whereas no correlation with PFS was evident. Grouping together those results allowed further patients stratification into 3 prognostic groups: favourable, intermediate and unfavourable. VEGF-A rs2010963 genotyping may represent an important tool for a more accurate selection of optimal candidates for regorafenib therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage*
  • Angiogenesis Inhibitors / pharmacology
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Female
  • Genotyping Techniques
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Pharmacogenomic Variants
  • Phenylurea Compounds / administration & dosage*
  • Phenylurea Compounds / pharmacology
  • Polymorphism, Single Nucleotide
  • Pyridines / administration & dosage*
  • Pyridines / pharmacology
  • Receptors, Fibroblast Growth Factor / genetics*
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor C / genetics*

Substances

  • Angiogenesis Inhibitors
  • Phenylurea Compounds
  • Pyridines
  • Receptors, Fibroblast Growth Factor
  • VEGFA protein, human
  • VEGFC protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor C
  • regorafenib