From the Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy; Ludwig Oncology Unit, Austin Hospital, Melbourne, Australia; National Oncological Institute, Klenová, Bratislava, Slovakia; Department of Oncology, Military Institute of Medicine, Warsaw, Poland; Department of Urology, Seoul National University College of Medicine, Seoul, Korea; The South West Wales Cancer Institute, Singleton Hospital, Swansea; Cancer Research UK, Department of Medical Oncology, University of Manchester; Christie Hospital National Health Services Foundation Trust, Manchester, United Kingdom; Oncology Research Unit, Oncology Service, Hospital Sao Lucas, Pontifícia Universidade Católica do Rio Grande do Sol, Porto Alegre, Brazil; Division of Medical Oncology and Hematology, Fundación Arturo López Pérez, Santiago, Chile; Chelyabinsk Regional Oncology Center, Chelyabinsk, Russian Federation; Krankenhaus Heitzing, mit Neurologischem Zentrum Rosenhugel, Vienna, Austria; Centro Médico San Roque, Tucumán, Argentina; GlaxoSmithKline, Collegeville, PA; and GlaxoSmithKline, Research Triangle Park, NC.
J Clin Oncol. 2023 Apr 10;41(11):1957-1964. doi: 10.1200/JCO.22.02622.
Pazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit. This randomized, double-blind, placebo-controlled phase III study evaluated efficacy and safety of pazopanib monotherapy in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC).
Adult patients with measurable, locally advanced, and/or metastatic RCC were randomly assigned 2:1 to receive oral pazopanib or placebo. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, tumor response rate (Response Evaluation Criteria in Solid Tumors), and safety. Radiographic assessments of tumors were independently reviewed.
Of 435 patients enrolled, 233 were treatment naive (54%) and 202 were cytokine pretreated (46%). PFS was significantly prolonged with pazopanib compared with placebo in the overall study population (median, PFS 9.2 4.2 months; hazard ratio [HR], 0.46; 95% CI, 0.34 to 0.62; < .0001), the treatment-naive subpopulation (median PFS 11.1 2.8 months; HR, 0.40; 95% CI, 0.27 to 0.60; < .0001), and the cytokine-pretreated subpopulation (median PFS, 7.4 4.2 months; HR, 0.54; 95% CI, 0.35 to 0.84; < .001). The objective response rate was 30% with pazopanib compared with 3% with placebo ( < .001). The median duration of response was longer than 1 year. The most common adverse events were diarrhea, hypertension, hair color changes, nausea, anorexia, and vomiting. There was no evidence of clinically important differences in quality of life for pazopanib versus placebo.
Pazopanib demonstrated significant improvement in PFS and tumor response compared with placebo in treatment-naive and cytokine-pretreated patients with advanced and/or metastatic RCC.
帕唑帕尼是一种口服血管生成抑制剂，针对血管内皮生长因子受体、血小板衍生生长因子受体和 c-Kit。这项随机、双盲、安慰剂对照的 III 期研究评估了帕唑帕尼单药治疗在初治和细胞因子预处理的晚期肾细胞癌（RCC）患者中的疗效和安全性。
可测量的局部晚期和/或转移性 RCC 成年患者被随机分配 2:1 接受口服帕唑帕尼或安慰剂。主要终点是无进展生存期（PFS）。次要终点包括总生存期、肿瘤反应率（实体瘤反应评价标准）和安全性。肿瘤的放射学评估由独立审查。
在纳入的 435 名患者中，233 名是初治患者（54%），202 名是细胞因子预处理患者（46%）。与安慰剂相比，帕唑帕尼在总体研究人群中显著延长了 PFS（中位 PFS：9.2 vs 4.2 个月；风险比[HR]，0.46；95%CI，0.34 至 0.62； <.0001）、初治亚组（中位 PFS：11.1 vs 2.8 个月；HR，0.40；95%CI，0.27 至 0.60； <.0001）和细胞因子预处理亚组（中位 PFS：7.4 vs 4.2 个月；HR，0.54；95%CI，0.35 至 0.84； <.001）。与安慰剂相比，帕唑帕尼的客观缓解率为 30%，而安慰剂为 3%（ <.001）。反应持续时间的中位数超过 1 年。最常见的不良反应是腹泻、高血压、头发颜色改变、恶心、厌食和呕吐。帕唑帕尼与安慰剂在生活质量方面没有临床意义上的差异。
与安慰剂相比，帕唑帕尼在初治和细胞因子预处理的晚期和/或转移性 RCC 患者中显著改善了 PFS 和肿瘤反应。
