Genetic polymorphisms as predictive biomarker of survival in patients with gastrointestinal stromal tumors treated with sunitinib.

ABSTRACT

This study aimed to identify single-nucleotide polymorphisms (SNPs) that are associated with outcome to treatment with sunitinib in patients with advanced gastrointestinal stromal tumors (GIST). Forty-nine SNPS involved in the pharmacokinetic and pharmacodynamic pathway of sunitinib were associated with progression-free survival (PFS) and overall survival (OS) in 127 patients with advanced GIST who have been treated with sunitinib. PFS was significantly longer in carriers of the TT genotype in POR rs1056878 (hazards ratio (HR) 4.310, 95% confidence interval (CI)1.457-12.746, P=0.008). The presence of the T-allele in SLCO1B3 rs4149117 (HR 2.024, 95% CI1.013-4.044, P=0.046), the CCC-CCC alleles in SLC22A5 haplotype (HR 2.603, 95% CI 1.216-5.573, P=0.014), and the GC-GC alleles in the IL4 R haplotype (HR 7.131, 95% CI1.518-33.496, P=0.013) were predictive for OS. This shows that polymorphisms in the pharmacokinetic and pharmacodynamic pathways of sunitinib are associated with survival in GIST. This may help to identify patients that benefit more from treatment with sunitinib.