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Pharmacogenet Genomics. 2017 Jun;27(6):227-231. doi: 10.1097/FPC.0000000000000280.

Evaluation of KDR rs34231037 as a predictor of sunitinib efficacy in patients with metastatic renal cell carcinoma.

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aHereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO) bOncology Department, Hospital Universitario 12 de Octubre cSpanish Oncology Genitourinary Group (SOGUG) dISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain eDepartment of Clinical Pharmacy and Toxicology fDepartment of Medical Oncology gDepartment of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden hDepartment of Medical Oncology, VU University Medical Center, Amsterdam iDepartment of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands jDepartment of Solid Tumour Oncology, Cleveland Clinic Foundation (CCF) Taussig Cancer Institute, Cleveland, Ohio, USA.


The identification of biomarkers able to predict clinical benefit from vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors is urgently needed. Recently, Maitland and colleagues described an association between KDR-rs34231037 and soluble VEGFR2 levels as well as pazopanib pharmacodynamics. We investigated in a well-characterized series of metastatic clear cell renal cell carcinoma patients whether rs34231037 could influence sunitinib response. Clinical data and DNA were available from an international series of 276 patients. KDR-rs34231037 association with sunitinib response, clinical benefit, and progression-free survival was analyzed using logistic and Cox regression analyses. We found that G-allele carriers were over-represented among patients with clinical benefit during sunitinib treatment compared with those refractory to the treatment (odds ratio: 3.78; 95% confidence interval: 1.02-14.06; P=0.047, multivariable analysis). In conclusion, rs34231037 variant carriers seemed to have better sunitinib response than wild-type patients. Moreover, the association with tumor size reduction suggests that this single nucleotide polymorphism might also identify patients with successful tumor downsizing under anti-VEGFR therapy.

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