Background: Tivozanib-TIVO is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR1), VEGFR-2, and VEGFR-3. TIVO was recently approved in Europe for the first line treatment of metastatic Renal Cell Carcinoma-RCC after a randomized trial demonstrated improved PFS and different safety profile compared to sorafenib. Methods: Retrospective analysis of safety and activity of TIVO administered within a compassionate use program to pts with metastatic RCC with no prior systemic treatment. Results: From Aug 2018 to Apr 2019, 64 pts have started TIVO at 1,34 mg daily (three weeks on, 1 week off) in 9 Italian Oncology Units. Median age was 67.5 years (range 40 to 85), 61% males, median creatinine clearance 63 ml/min(range 30-97). According to IDMC criteria, 27.5 % of pts were good prognosis, 60% intermediate and 10.5 % poor. Primary tumor had been removed in 70.5% of pts. Histology was clear cell 89.5%, papillary 4.5%, unclassified 6%. Response rate was 46.5%, stable disease 37.5%, progression 16%. Grade 3-4 toxicities were 4.5% hypertension, 3% mucositis, 1.5% diarrhea and 1.5% anorexia. Dose reduction to 0.89 mg was applied to 15.5% of pts. PFS and OS data will be presented at the Meeting. Conclusions: TIVO showed good activity and favorable safety profile in a real world cohort of unselected pts with metastatic RCC. Predictive biomarkers of response to antiangiogenic therapy are urgently needed in order to identify RCC pts who should receive VEGFR inhibitors in the first line.