Fibroblast Growth Factor Receptor-2 Polymorphism rs2981582 is Correlated With Progression-free Survival and Overall Survival in Patients With Metastatic Clear-cell Renal Cell Carcinoma Treated With Sunitinib

Clin Genitourin Cancer. 2019 Apr;17(2):e235-e246. doi: 10.1016/j.clgc.2018.11.002. Epub 2018 Nov 16.


Background: There are no validated markers that predict response or resistance in patients with metastatic clear-cell renal cell carcinoma (mccRCC) treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors such as sunitinib and pazopanib. Recently, single nucleotide polymorphism (SNP) rs2981582 in Fibroblast Growth Factor Receptor 2 (FGFR2) was found to be associated with clinical outcome in patients with mccRCC treated with pazopanib and sunitinib. We aimed to validate these findings in patients treated with sunitinib.

Materials and methods: Germline DNA was collected in patients with mccRCC starting first-line systemic therapy with sunitinib. SNP rs2981582 in FGFR2 C>T was genotyped. Association of the genotype with response rate, tumor shrinkage, median progression-free survival (mPFS), and median overall survival (mOS) was studied.

Results: We collected clinical data from 154 patients with available germline DNA. Baseline prognostic markers were well-balanced between both subgroups. Patients with the TT genotype had a poorer outcome compared with patients with the CT/CC genotype. The median shrinkage of selected tumor target lesions during treatment with sunitinib was -16% versus -31% (P = .002), mPFS was 8 versus 15 months (P = .0007), and mOS was 22 versus 33 months (P = .04), respectively. On multivariate analysis, rs2981582 remained an independent predictor of PFS (hazard ratio, 2.858; 95% confidence interval, 1.659-4.923; P < .0001) and OS (hazard ratio, 1.795; 95% confidence interval, 1.003-3.212; P = .049).

Conclusion: Polymorphism rs2981582 in FGFR2 is correlated to PFS and OS in patients with mccRCC treated with sunitinib. Prospective validation of the impact of this SNP is warranted.

Keywords: Angiogenesis inhibitor; Biomarker; Outcome; Prognosis; Single nucleotide polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / genetics
  • Disease-Free Survival
  • Female
  • Genotype
  • Germ-Line Mutation
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / genetics
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / therapeutic use
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics*
  • Retrospective Studies
  • Sunitinib / administration & dosage*
  • Sunitinib / therapeutic use
  • Treatment Outcome


  • Protein Kinase Inhibitors
  • FGFR2 protein, human
  • Receptor, Fibroblast Growth Factor, Type 2
  • Sunitinib