title: VEGFR1 single nucleotide polymorphisms associated with outcome in patients with metastatic renal cell carcinoma treated with sunitinib - a multicentric retrospective analysis.
abstract: BACKGROUND
  There are no validated markers that predict outcome in metastatic renal cell cancer (mRCC) patients treated with sunitinib. Recently, single nucleotide polymorphism (SNP) rs9582036 in VEGFR1 has been proposed as a predictor of progression-free survival (PFS) and overall survival (OS) to bevacizumab in patients with pancreatic cancer and rs7993418 in VEGFR1 as predictor for PFS in mRCC-patients treated with bevacizumab. Here, we aim to study the impact of these SNPs in mRCC patients treated with sunitinib.
  
  
  METHODS
  We included patients with mRCC treated in 15 institutions in France and Belgium. Patients received sunitinib as first-line targeted therapy. We assessed response, time-to-tumor progression (TTP), OS, and clinical and biochemical parameters associated with outcome. We genotyped rs9582036 and rs7993418 as well as three other surrounding SNPs in VEGFR1: rs9554320, rs9554316 and rs9513070. Association between SNPs and treatment outcome were studied by univariate analysis and by multivariate Cox regression using relevant clinical factors associated with TTP and OS as covariates.
  
  
  RESULTS
  Ninety-one patients were included. We found that mRCC patients with the CC-variant in rs9582036 in VEGFR1 have a poorer response rate (RR) (0% vs. 46%, p = 0.028), a poorer PFS (10 vs. 18 months, p = 0.033 on univariate and 0.06 on multivariate analysis) and a poorer OS (14 vs. 31 months, p = 0.019 on univariate and 0.008 on multivariate analysis) compared to patients with the AC- and AA-genotypes. mRCC patients with the AA-variant in rs9554320 in VEGFR1 have a poorer PFS (12 vs. 21 months, p = 0.0066 on univariate and 0.005 on multivariate analysis) and a poorer OS (22 vs. 34 months, p = 0.019 on univariate and 0.067 on multivariate analysis) compared to patients with the AC- and CC-genotypes. Interpretation. mRCC patients with the CC-genotype in VEGFR1 SNP rs9582036 have a poorer response rate, PFS and OS when treated with sunitinib. These findings are in agreement with the association of rs9582036 and outcome observed in bevacizumab treated pancreatic cancer patients. Prospective validation of this SNP is warranted.
authors: Department of General Medical Oncology and Laboratory for Experimental Oncology, University Hospitals Leuven, Leuven Cancer Institute , KU Leuven, Leuven , Belgium.
authors: Benoit
authors: B
authors: Beuselinck
authors: Alexandra
authors: A
authors: Karadimou
authors: Diether
authors: D
authors: Lambrechts
authors: Bart
authors: B
authors: Claes
authors: Pascal
authors: P
authors: Wolter
authors: Gabrielle
authors: G
authors: Couchy
authors: Joost
authors: J
authors: Berkers
authors: Hendrik
authors: H
authors: van Poppel
authors: Robert
authors: R
authors: Paridaens
authors: Patrick
authors: P
authors: Schöffski
authors: Arnaud
authors: A
authors: Méjean
authors: Virginie
authors: V
authors: Verkarre
authors: Evelyne
authors: E
authors: Lerut
authors: Florence
authors: F
authors: Joly
authors: Thierry
authors: T
authors: Lebret
authors: Gwénaelle
authors: G
authors: Gravis
authors: Gael
authors: G
authors: Deplanque
authors: Aurélien
authors: A
authors: Descazeaud
authors: Nathalie Rioux
authors: NR
authors: Leclercq
authors: Vincent
authors: V
authors: Molinié
authors: Jean-Jacques
authors: JJ
authors: Patard
authors: Corine
authors: C
authors: Teghom
authors: Reza
authors: R
authors: Elaidi
authors: Jessica
authors: J
authors: Zucman-Rossi
authors: Stéphane
authors: S
authors: Oudard
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011758:Pyrroles / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077210:Sunitinib; D015996:Survival Rate; D016896:Treatment Outcome; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D011758:Pyrroles; D040281:Vascular Endothelial Growth Factor Receptor-1; D000077210:Sunitinib