Work

Meta-analysis on the association of VEGFR1 genetic variants with sunitinib outcome in metastatic renal cell carcinoma patients

Year: 2016

Type: article

Abstract: // Xiaoyan Liu 1, 2 , Jesse J. Swen 1 , Epie Boven 3 , Daniel Castellano 4, 5 , Hans Gelderblom 6 , Ron H.J. Mathijssen 7 , Cristina Rodríguez-Antona 8, 9 , Jesus García-Donas 5, 10 , Brian I. Rini 11 , Henk-Jan Guchelaar 1 1 Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands 2 Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, China 3 Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands 4 Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain 5 Spanish Oncology Genitourinary Group (SOGUG), Madrid, Spain 6 Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands 7 Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands 8 Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain 9 ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain 10 Oncology Unit, Clara Campal Comprehensive Cancer Center, Madrid, Spain 11 Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute (CCF), Cleveland, Ohio, USA Correspondence to: Henk-Jan Guchelaar, email: [email protected] Keywords: sunitinib, metastatic renal cell carcinoma, VEGFR1 , validation study, meta-analysis Received: August 20, 2016 Accepted: November 07, 2016 Published: November 25, 2016 ABSTRACT VEGFR1 rs9582036 and rs9554320 were previously reported the association with sunitinib progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC). Hereafter, the association of both single nucleotide polymorphisms (SNPs) with PFS/OS was confirmed in two independent mRCC cohorts. The aim of the current study was to validate the associations of both SNPs with sunitinib outcome in three independent well-characterized cohorts (SUTOX, CCF and SOGUG) including 286 sunitinib-treated mRCC patients, as well as to perform a meta-analysis of current and published data combined. We found that rs9582036 and rs9554320 showed a significant association with sunitinib PFS in the CCF cohort (HR: 0.254, 95%CI: 0.092-0.703; P=0.008 and HR: 0.430, 95%CI: 0.200-0.927; P=0.031, respectively). Patients with the variant genotype of rs9582036 and rs9554320 had a shorter median PFS. No significant association of both SNPs with sunitinib PFS or OS was detected in either the SUTOX or SOGUG cohort. After the combination of all available data into a meta-analysis, the association of both SNPs with sunitinib PFS or OS did not achieve the threshold for statistical significance. Our findings suggest that, although VEGFR1 rs9582036 and rs9554320 are involved in sunitinib therapy outcome, its clinical use as biomarkers for prediction of sunitinib outcome in mRCC patients is limited, due to inconsistent findings when analyzing all existing studies together.

Source: Oncotarget

DOI: 10.18632/oncotarget.13597