Angiogenesis genotyping in the selection of first-line treatment with either sunitinib or pazopanib for advanced renal cell carcinoma

Oncotarget. 2016 Jun 21;7(25):37599-37607. doi: 10.18632/oncotarget.9229.

Abstract

Introduction: Recent data from the COMPARZ study seem to suggest a non-inferiority of pazopanib confronted with sunitinib in PFS and OS. We previously reported how VEGF and VEGFR polymorphisms might have a predictive role in patients treated with first-line sunitinib. Aim of our study was to investigate whether tumour angiogenesis genotyping could influence clinical outcome in RCC patients treated with either sunitinib or pazopanib, in order to help clinicians select the appropriate treatment for each patient.

Results: 19 patients were treated with pazopanib while 78 received sunitinib. VEGF A rs833061 resulted significant in PFS in sunitinib vs pazopanib patients (CC+CT>TT in sunitinib, TT>CC+CT in pazopanib; p<0,0001); VEGF A rs2010963 resulted significant in PFS in sunitinib vs pazopanib patients (GG+CG>CC in sunitinib, CC>GG+CG in pazopanib; p<0,0001); VEGF A rs699947 resulted significant in PFS in sunitinib vs pazopanib patients (AA+AC>CC in sunitinib, CC>AA+AC in pazopanib; p<0,0001). OS showed no statistically significant difference.

Conclusions: in our analysis patients with opposite polymorphisms of rs833061, rs2010963, rs699947 of VEGF A seems to have a better PFS if treated with either sunitinib or pazopanib. Our data seem to suggest that biology could have a role choosing first line treatment for mRCC patients.

Methods: a retrospective analysis on 97 histologic samples of mRCC patients was conducted for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs).

Keywords: VEGF; angiogenesis; pazopanib; renal cell carcinoma; sunitinib.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use*
  • Carcinoma, Renal Cell / blood supply*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / pathology
  • Female
  • Genotype
  • Humans
  • Indazoles
  • Indoles / therapeutic use*
  • Kidney Neoplasms / blood supply*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / genetics
  • Polymorphism, Single Nucleotide
  • Pyrimidines / therapeutic use*
  • Pyrroles / therapeutic use*
  • Receptors, Vascular Endothelial Growth Factor / genetics
  • Retrospective Studies
  • Sulfonamides / therapeutic use*
  • Sunitinib
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Angiogenesis Inhibitors
  • Indazoles
  • Indoles
  • Pyrimidines
  • Pyrroles
  • Sulfonamides
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • pazopanib
  • Receptors, Vascular Endothelial Growth Factor
  • Sunitinib