XXXX and @entity1262 polymorphisms as predictors for sunitinib outcome in @entity1358 .

@entity1 @entity1262 @entity137 @entity5396 @entity1358 @entity49139
BACKGROUND: In our exploratory studies, we associated single nucleotide polymorphisms (SNPs) in candidate genes with the efficacy and @entity137 of sunitinib in @entity1358 ( @entity1358 ). OBJECTIVE: To see whether previously reported associations of SNPs with sunitinib-induced @entity137 and efficacy in @entity1358 can be confirmed in a large cohort of @entity1 . DESIGN, SETTING, AND @entity1 : The @entity1358 @entity1 treated with sunitinib and a DNA sample available were pooled from three exploratory studies conducted in the United States, Spain, and the Netherlands. A total of 22 SNPs and 6 haplotypes in 10 candidate genes related to the pharmacokinetics and pharmacodynamics of sunitinib were selected for association testing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: SNPs and haplotypes were tested for associations with @entity137 , dose reductions, progression-free survival (PFS), overall survival (OS), and best objective response. RESULTS AND LIMITATIONS: A total of 333 @entity1 were included. We confirmed 2 of the 22 previously reported SNP associations. The presence of @entity5396 *1 was associated with dose reductions (odds ratio: 2.0; 95% confidence interval [CI], 1.0-4.0, p=0.039). The presence of @entity49139 in the @entity1262 haplotype was associated with an increased PFS (hazard ratio: 1.9; 95% CI, 1.3-2.6; p<0.001) and remained significant after Bonferroni correction. These associations are consistent with prior observations. CONCLUSIONS: The confirmation of previously reported associations between polymorphisms in @entity5396 and @entity1262 with sunitinib @entity137 and efficacy, respectively, indicates that genotyping of these genetic variants will be useful for guiding sunitinib treatment. A prospective validation study is needed to confirm our findings on @entity1262 and @entity5396 genetic polymorphisms. @entity1 SUMMARY: We confirmed that variants in genes involved in processing sunitinib through the body have an effect on sunitinib treatment outcome. These findings confirm the potential of testing for these genetic variants to improve individual @entity1 care for @entity1 with @entity1358 treated with sunitinib.
