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Validation of VEGFR 1 rs9582036 as predictive biomarker in metastatic clear‐cell renal cell carcinoma patients treated with sunitinib
Author(s) -
Beuselinck Benoit,
JeanBaptiste Johnny,
Schöffski Patrick,
Couchy Gabrielle,
Meiller Clément,
Rolland Frederic,
Allory Yves,
Joniau Steven,
Verkarre Virginie,
Elaidi Reza,
Lerut Evelyne,
Roskams Tania,
Patard JeanJacques,
Oudard Stephane,
Méjean Arnaud,
Lambrechts Diether,
ZucmanRossi Jessica
Publication year - 2016
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/bju.13585
Subject(s) - sunitinib , medicine , renal cell carcinoma , cohort , oncology , proportional hazards model , clear cell renal cell carcinoma , biomarker , progression free survival , gastroenterology , overall survival , biology , biochemistry
Objectives To validate vascular endothelial growth factor receptor‐1 ( VEGFR 1) single nucleotide polymorphism ( SNP ) rs9582036 as a potential predictive biomarker in metastatic clear‐cell renal cell carcinoma (m‐cc RCC ) patients treated with sunitinib. Materials and Methods m‐cc RCC 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 VEGFR 1 SNP s: 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 VEGFR 1 rs9582036 is a candidate predictive biomarker in m‐cc RCC ‐patients treated with sunitinib.