Video: VEGFR1 rs9582036 as a predictive biomarker in m-ccRCC patients treated with sunitinib

Validation of VEGFR1 rs9582036 as predictive biomarker in metastatic clear-cell renal cell carcinoma patients treated with sunitinib

Benoit Beuselinck*,†,‡, Johnny Jean-Baptiste*,†, Patrick Schoffski‡, Gabrielle Couchy*,†, Clement Meiller*,†, Frederic Rolland§, Yves Allory¶, Steven Joniau**, Virginie Verkarre††, Reza Elaidi‡‡, Evelyne Lerut§§, Tania Roskams§§, Jean-Jacques Patard¶¶, Stephane Oudard†,‡‡, Arnaud Mejean***, Diether Lambrechts†††,‡‡‡ and Jessica Zucman-Rossi*,†,‡‡

*Inserm, UMR-1162, Genomique fonctionnelle des tumeurs solides, IUH, Paris, †Sorbonne Paris Cite, Facultede Medecine, Universite Paris Descartes, Paris, France, ‡Department of General Medical Oncology and Laboratory for Experimental Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven, Leuven, Belgium, §Department of Medical Oncology, Institut de Cancerologie de l’Ouest, Saint Herblain, ¶Department of Pathology, Assistance Publique-Hopitaux de Paris, Hopital Henri Mondor, Creteil, France, **Department of Urology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven, Leuven, Belgium, ††Department of Pathology, Assistance Publique-Hopitaux de Paris, Hopital Necker-Enfants malades, Paris, ‡‡Department of Medical Oncology, Assistance Publique-Hopitaux de Paris, Hopital Europeen Georges Pompidou, Paris, France, §§Department of Pathology, University Hospitals Leuven, KU Leuven, Leuven, Belgium, ¶¶Department of Urology, Hopital Bicetre, Le Kremlin-Bicetre, ***Department of Urology, Assistance Publique-Hopitaux de Paris, Hopital Europeen Georges Pompidou, Paris, France, †††Laboratory for Translational Genetics, Department of Oncology, KU Leuven, Leuven, and ‡‡‡Vesalius Research Center, VIB, Leuven, Belgium

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Abstract

Objectives

To validate vascular endothelial growth factor receptor-1 (VEGFR1) single nucleotide polymorphism (SNP) rs9582036 as a potential predictive biomarker in metastatic clear-cell renal cell carcinoma (m-ccRCC) patients treated with sunitinib.

Materials and Methods

m-ccRCC patients receiving sunitinib as first-line targeted therapy were included. We assessed response rate (RR), progression-free survival (PFS), overall survival (OS), and clinical and biochemical parameters associated with outcome. We genotyped five VEGFR1 SNPs: rs9582036, rs7993418, rs9554320, rs9554316 and rs9513070. Association with outcome was studied by univariate analysis and by multivariate Cox regression. Additionally, we updated survival data of our discovery cohort as described previously.

Results

Sixty-nine patients were included in the validation cohort. rs9582036 CC-carriers had a poorer PFS (8 vs 12 months, P = 0.02) and OS (11 vs 27 months, P = 0.003) compared to AC/AA-carriers. rs7993418 CC-carriers had a poorer OS (8 vs 24 months, P = 0.004) compared to TC/TT-carriers. rs9554320 AA-carriers had a poorer RR (0% vs 53%, P = 0.009), PFS (5 vs 12 months, P = 0.003) and OS (10 vs 25 months, P = 0.004) compared to AC/CC-carriers. When pooling patients from the discovery cohort, as described previously (n = 88), and the validation cohort, in the total series of 157 patients, rs9582036 CC-carriers had a poorer RR (8% vs 49%, P = 0.004), PFS (8 vs 14 months, P = 0.003) and OS (13 vs 30 months, P = 0.0004) compared to AC/AA-carriers. Unfavorable prognostic markers at start of sunitinib were well balanced between rs9582036 CC- and AC/AA-carriers.

Conclusion

VEGFR1 rs9582036 is a candidate predictive biomarker in m-ccRCC-patients treated with sunitinib.