(UroToday.com) Sunitinib was standard first line treatment for metastatic clear cell renal cell carcinoma (mccRCC) for many years until multiple clinical trials showed superior efficacy of various treatment combinations including nivolumab and ipilimumab in International Metastatic RCC Database Consortium (IMDC) intermediate or poor-risk disease. Combination nivolumab and ipilimumab resulted in a 42% objective response rate and median progression-free survival of 11.6 months. Single-agent nivolumab is associated with an objective response rate of 28.7% with a median progression-free survival of 5.54 months. A recent transcriptomic analysis of primary frozen ccRCC specimens revealed 4 molecular subgroups that could be summarized by a 35 gene signature (ccrcc1-ccrcc4). Ccrcc1 (immune-low) and ccrcc4 (immune-high) were associated with the poorest outcomes to sunitinib, whereas ccrcc2 (angio-high) and ccrcc3 (normal-like) had the best outcomes. The authors of this presentation hypothesized that these expression signatures could stratify patients most likely to respond to sunitinib (ccrcc2, angio-high, and ccrcc3), nivolumab (ccrcc4,immune-high), and nivolumab and ipilimumab (ccrcc1, immune-low).