Benoit Beuselinck1,2,3, Johnny Jean-Baptiste1,2, Patrick Schöffski3, Gabrielle Couchy1,2, Clément Meiller1,2, Frederic Rolland4, Yves Allory5, Steven Joniau6, Virginie Verkarre7, Reza Elaidi8, Evelyne Lerut9, Tania Roskams9, Jean-Jacques Patard10, Stephane Oudard2,8, Arnaud Méjean11, Diether Lambrechts12,13, Jessica Zucman-Rossi1,2,8. 1. Inserm, UMR-1162, Génomique fonctionnelle des tumeurs solides, IUH, Paris, France. 2. Sorbonne Paris Cité, Faculté de Médecine, Université Paris Descartes, Paris, France. 3. Department of General Medical Oncology and Laboratory for Experimental Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven, Leuven, Belgium. 4. Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Saint Herblain, France. 5. Department of Pathology, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil, France. 6. Department of Urology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven, Leuven, Belgium. 7. Department of Pathology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants malades, Paris, France. 8. Department of Medical Oncology, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France. 9. Department of Pathology, University Hospitals Leuven, KU Leuven, Leuven, Belgium. 10. Department of Urology, Hôpital Bicêtre, Le Kremlin-Bicêtre, France. 11. Department of Urology, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France. 12. Laboratory for Translational Genetics, Department of Oncology, KU Leuven, Leuven, Belgium. 13. Vesalius Research Center, VIB, Leuven, Belgium.
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.
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:VEGFR1rs9582036 is a candidate predictive biomarker in m-ccRCC-patients treated with sunitinib.
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