Activating genomic mutations in the mTOR pathway to predict responses to everolimus and temsirolimus in patients with metastatic renal cell carcinoma (mRCC): Results from a large multi-institutional cohort.

4519 Background: Mammalian target of rapamycin (mTOR) inhibitors are approved in mRCC, but only a subset of patients derives clinical benefit. Recently, case reports have suggested that mutations in mTOR pathway genes might be associated with response to everolimus and temsirolimus in several malignancies, including mRCC. Methods: We amassed a large international cohort of mRCC patients with available tumor specimens who received mTOR inhibitors and had distinct clinical outcomes: responders were defined as complete response (CR), partial response (PR) or stable disease with any tumor shrinkage or no tumor growth for at least 6 months (R); non-responders were defined as disease progression within the first 3 months of therapy (NR). Tumor DNA from 94 patients was analyzed using a targeted next-generation sequencing panel covering 504 cancer genes. We performed a blinded analysis to investigate the correlation between mutations in mTOR pathway genes and response status. Results: Samples from 79 of 94 patien...