Association of inherited genetic variation with clinical outcome in patients with advanced renal cell carcinoma treated with mTOR inhibition.

4543 Background: Mammalian target of rapamycin (mTOR)-targeted therapy is standard in patients with metastatic renal cell carcinoma (mRCC). Predictive biomarkers for response are lacking. We sought to characterize outcome after mTOR inhibition based on germline variation in 2 critical genes in the mTOR pathway: phosphoinositide-3-kinase catalytic alpha (PIK3CA) and mTOR. Methods: 76 Americans of European ancestry treated with temsirolimus or everolimus for mRCC were included. Germline DNA was genotyped for all common genetic variation (minor allele frequency [MAF] >0.05) across PIK3CA and mTOR, tagging with single nucleotide polymorphisms (SNPs) at r2>0.8. Associations between genotype and progression-free survival (PFS) and overall survival (OS) from the start of mTOR-targeted therapy were measured using univariate Cox model. Results: Among 76 patients, 66% were poor or intermediate risk and 89% received prior systemic therapies. Median follow up was 23.7 months. Median PFS and OS were 4.3 and 12.7 month...