Background: Fourthline targeted therapy efficacy in mRCC is not well characterized and is not reimbursed in many jurisdictions worldwide. Methods: The IMDC consists of consecutive patient series from 35 international cancer centers. It was queried for mRCC patients who received fourth line targeted therapy. Kaplan Meier estimates were used for time to treatment failure (TTF) and overall survival (OS). Results: 594 out of 7498 (8%) mRCC patients initially treated with first line targeted therapy eventually received fourth line therapy from a class of approved agents. Baseline characteristics are displayed in Table 1. The most common fourth line therapies were everolimus 17%, sorafenib 15%, axitinib 13%, pazopanib 13%, sunitinib 13%, nivolumab 7%. IMDC prognostic group distributions (Heng et al JCO 2009) and their associated survivals (both determined from fourth line therapy initiation) were 5% favorable risk (OS 23.1 (14.7-not reached)), 66% intermediate risk (OS 13.8 (11.4-17.5)), and 29% poor risk (OS 7.8 (4.93-12.2)) (OS p<0.0001). Overall response rate for fourth-line therapy was 12.5% and 41.5% had stable disease in those patients that were evaluable (n=407). Median TTF on fourth line therapy was 4.40 months (95% CI 3.98-5.06) and median OS from fourth line therapy initiation was 12.8 months (95% CI 11.4-14.4). Conclusions: Fourth line targeted therapy has demonstrated activity, is uncommon, and should be offered to clinically eligible patients. Further studies are required to determine appropriate sequencing. IMDC criteria appear to stratify favorable/intermediate/poor risk patients well in the fourth line setting.