Transcriptomic Profiling of the Tumor Microenvironment Reveals Distinct Subgroups of Clear cell Renal Cell Cancer - Data from a Randomized Phase III Trial [Research Articles]

Metastasis remains the main reason for renal cell carcinoma (RCC)-associated mortality. Tyrosine kinase inhibitors (TKI) impart clinical benefit for most RCC patients but the determinants of response are poorly understood. We report an integrated genomic and transcriptomic analysis of metastatic clear cell RCC (ccRCC) patients treated with TKI therapy and identify predictors of response. Patients in the COMPARZ phase III trial received first-line sunitinib or pazopanib with comparable efficacy. RNA-based analyses revealed four distinct molecular subgroups associated with response and survival. Characterization of these subgroups identified mutation profiles, angiogenesis and macrophage infiltration programs to be powerful predictors of outcome with TKI therapy. Notably, predictors differed by the type of TKI received. Our study emphasizes the clinical significance of angiogenesis and immune tumor microenvironment and suggests the critical effects its various aspects have on TKI efficacy vary by agent. This has broad implications for optimizing precision treatment of RCC.

http://bit.ly/2TxdpQ8