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Aim: New targeted therapeutics approved for mRCC offer multiple options in each line (L) of treatment (tto). Approximately 10-15% of mRCC p are treated with a 3rd L target agent. However, there are few data about which is the most appropriate strategy in the sequential tto in these p. Our aim is to analyze the efficacy of these strategies in terms of overall survival (OS). Methods: P diagnosed with mRCC from January 2005 to December 2013 in 3 multidisciplinary centres of Spain were retrospectively studied. Therapies were classified as: vascular endothelial growth factor receptor inhibitors (VEGFi) or mamaliam target of rapamycin inhibitors (mTORi). P were classified into subgroups depending on which strategy of tto they received: VEGFi-VEGFi-VEGFi, VEGFi-mTOR-VEGFi or VEGFi-VEGFi-mTOR. Analyses OS curve and medians were estimated using Kaplan Meier Method. Results: 279p were diagnosed with mRCC. P characteristics were: mean age 61.07y; 69.5% males, 29% females; Histology: 79.2% Clear Cell (CC), 7.2% Papilar, 3.2% Chromophob, 7.2% others; Prognosis: 13.6% poor, 49.1% Intermediate, 34.1% Good; 76.3% Prior nephrectomy. 97.5% (272p) of p received at least 1L of tto, 40% (109p) 2nd L and 16.5% (45p) 3rd L. 78.37% of p from the group of VEGFi-VEGFi tto recived a 3rd L (27% VEGFi and 51% mTORi) in front of 56% from VEGFi-mTOR (all VEGFi as 3rd L). OS of all p was 25 months (m) 95%CI(17.8-32.23). OS from p who only recived 2nd L were: VEGFi-mTOR 20m 95%CI(4.63-35.38); VEGFi-VEGFi 32m 95%CI(8.67-55.33). OS for 3rd L of tto were: VEGFi-mTOR-VEGFi 35m 95%CI(15.05-54.95); VEGFi-VEGFi-mTOR 30m 95%CI(19.37-40.68); VEGFi-VEGFi-VEGFi not reached. Conclusions: Results suggest that sequence with VEGFi has a trend in better outcomes: median OS has not been reached in VEGFi-VEGFi-VEGFi subgroup at the time of analyses and OS from 3rd L subgroups treated with an mTORi was similar than p receiving only 2nd L with two VEGFi. However, the study is limited by unbalanced factors and small number of p. More details of p characteristics subgroups will be provided. Disclosure: All authors have declared no conflicts of interest.