Temsirolimus has long been the only approved first-line standard-of-care (SOC) with overall survival (OS) benefit in poor-risk patients with advanced or metastatic renal cell cancer (mRCC). However, tyrosine kinase inhibitors are also commonly used in clinical practice. Pazopanib is a SOC for first-line mRCC treatment, but for poor-risk patients data are scarce. The FLIPPER study aimed to assess efficacy and safety of first-line pazopanib in poor-risk mRCC patients. FLIPPER was a single-arm, multicenter, phase IV trial. Key inclusion criteria were treatment-naive clear cell, inoperable advanced or mRCC, poor-risk according to MSKCC with slight modification, Karnofsky performance status (KPS) ≥60%, and adequate organ function. Oral pazopanib 800 mg was given daily. Primary endpoint was the 6-month progression-free survival rate (PFS6). Secondary endpoints included PFS, OS, overall response rate (ORR), duration of response (DOR), and safety. For analysis, descriptive statistics were used. Between 2012-2016, 60 patients had been included. 43 patients qualified for safety analyses, 34 for efficacy. Median age was 66 years, 64.7% of patients were poor-risk, 82.4% had a KPS ≤70%. PFS6 was 35.3% (95% CI, 19.7-53.5). Median PFS and OS were 4.5 months (95% CI, 3.6-7.8) and 9.3 months (95% CI, 6.6-22.2), respectively. ORR was 32.4% (95% CI, 17.4-50.5), median DOR 9.7 months (95% CI, 1.8-12.4). The most common treatment-related grade 3/4 adverse event reported in 4.7% of patients was hypertension. No treatment-related death occurred. Since pazopanib is active and well-tolerated in poor-risk patients with clear cell mRCC, our results support its use as first-line treatment in this setting. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.