Department of Urology, Interdisciplinary Center of Renal Tumors, Ludwig-Maximilians-University of Munich, Munich, Germany.
Department of Urology, West German Cancer Center, University of Duisburg-Essen, University Hospital Essen, Essen, Germany.
Int J Cancer. 2021 Feb 15;148(4):950-960. doi: 10.1002/ijc.33238. Epub 2020 Aug 18.
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 an SOC for first-line mRCC treatment, but for poor-risk patients data are scarce. The FLIPPER (First-Line Pazopanib in Poor-Risk Patients with Metastatic Renal Cell Carcinoma) 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 and 2016, 60 patients had been included. Forty-three 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.
替西罗莫司长期以来一直是唯一被批准用于治疗高危转移性肾细胞癌（mRCC）患者的一线标准治疗（SOC）药物，具有总生存期（OS）获益。然而，酪氨酸激酶抑制剂在临床实践中也经常被使用。帕唑帕尼是一线 mRCC 治疗的 SOC，但对于高危患者的数据很少。FLIPPER（一线帕唑帕尼治疗高危转移性肾细胞癌）研究旨在评估一线帕唑帕尼治疗高危 mRCC 患者的疗效和安全性。FLIPPER 是一项单臂、多中心、IV 期试验。主要纳入标准为初治、不可切除的晚期或 mRCC、经轻微修改的 MSKCC 高危、卡氏功能状态（KPS）≥60%和足够的器官功能。每天口服 800mg 帕唑帕尼。主要终点为 6 个月无进展生存率（PFS6）。次要终点包括 PFS、OS、总缓解率（ORR）、缓解持续时间（DOR）和安全性。分析采用描述性统计。2012 年至 2016 年间，共纳入 60 例患者。43 例患者纳入安全性分析，34 例患者纳入疗效分析。中位年龄为 66 岁，64.7%的患者为高危，82.4%的患者 KPS≤70%。PFS6 为 35.3%（95%CI，19.7-53.5）。中位 PFS 和 OS 分别为 4.5 个月（95%CI，3.6-7.8）和 9.3 个月（95%CI，6.6-22.2）。ORR 为 32.4%（95%CI，17.4-50.5），中位 DOR 为 9.7 个月（95%CI，1.8-12.4）。4.7%的患者报告最常见的与治疗相关的 3/4 级不良事件是高血压。无治疗相关死亡。由于帕唑帕尼在透明细胞 mRCC 高危患者中具有活性且耐受性良好，我们的结果支持将其作为该人群的一线治疗药物。
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