Genetic polymorphisms of VEGFR2 and FGFR2 genes are associated with exposure to sunitinib and cardiovascular toxicity

PURPOSE: Sunitinib is a multikinase inhibitor used to treat metastatic renal cell carcinoma (mRCC), with an inter-individual variability of pharmacokinetics and toxicity. Our goal was to assess associations between the pharmacogenetics, pharmacokinetics and toxicity of sunitinib. METHODS: In this multi-center prospective study, 42 patients with mRCC were included. An NGS panel was used to identify variations in 19 genes involved in sunitinib pharmacokinetics and pharmacodynamics. Residual concentration of sunitinib and N-desethyl-sunitinib were used to estimate a composite AUC at steady-state. RESULTS: = 0.0002 respectively). CONCLUSION: We demonstrated for the first time, an association between genetics polymorphisms in sunitinib targets and extent of exposure to this molecule as well as their association associated with the risk of cardiovascular toxicity. We described the concentration dependence of neurological and endocrine toxicity. TRIAL REGISTRATION: NCT02404584, registered 26 March 2015.