The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
City of Hope Comprehensive Cancer Center, Duarte, California, USA.
Oncologist. 2018 May;23(5):540-555. doi: 10.1634/theoncologist.2017-0534. Epub 2018 Feb 27.
The management of advanced clear-cell renal cell carcinoma has steadily improved over the past decade with the introduction of antiangiogenic and targeted therapies. Recently, three new therapies have been approved for use as second-line options that further advance the treatment armamentarium: nivolumab, a monoclonal antibody targeting the programmed cell death receptor; cabozantinib, a small-molecule tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR), MET, and AXL; and lenvatinib, a small-molecule TKI of VEGF and fibroblast growth factor receptors that is used in combination with everolimus, an inhibitor of the mechanistic target of rapamycin. Together, these and previously approved second-line treatments offer clinicians the ability to better individualize treatment for patients after progression on first-line VEGFR-targeted therapies. In this comprehensive review, we discuss the efficacy and safety results from the pivotal trials of these newly approved therapies, including the quality of study design, the level of evidence, subgroup analyses, and how these data can help to guide clinicians to select the most appropriate second-line therapy for their patients.
This review article provides the reader with a comprehensive overview of current treatment options for patients with advanced clear-cell renal cell carcinoma (RCC) whose disease has progressed after their first therapy. As many patients with RCC experience disease progression with initial treatments, effective second-line therapies are critical. Nivolumab, cabozantinib, and lenvatinib plus everolimus have recently been approved as second-line treatments. The new agents discussed in this review increase the therapeutic options available and provide physicians with opportunities to individualize treatments for their patients, with a view to improving disease control and survival outcomes.
在过去十年中，随着抗血管生成和靶向治疗的引入，晚期透明细胞肾细胞癌的治疗得到了稳步改善。最近，又有三种新的治疗方法被批准作为二线选择，进一步推进了治疗手段：nivolumab，一种针对程序性细胞死亡受体的单克隆抗体；cabozantinib，一种血管内皮生长因子受体（VEGFR）、MET 和 AXL 的小分子酪氨酸激酶抑制剂（TKI）；以及 lenvatinib，一种与 everolimus 联合使用的 VEGF 和成纤维细胞生长因子受体的小分子 TKI，后者是一种雷帕霉素的机械靶点抑制剂。这些药物和以前批准的二线治疗方法一起，为临床医生在一线 VEGFR 靶向治疗进展后为患者提供了更好的个体化治疗能力。在这篇全面的综述中，我们讨论了这些新批准治疗方法的关键试验的疗效和安全性结果，包括研究设计的质量、证据水平、亚组分析，以及这些数据如何帮助指导临床医生为患者选择最合适的二线治疗方法。
这篇综述文章为读者提供了一个全面的概述，介绍了晚期透明细胞肾细胞癌（RCC）患者的当前治疗选择，这些患者在其首次治疗后疾病进展。由于许多 RCC 患者在初始治疗中经历疾病进展，因此有效的二线治疗方法至关重要。nivolumab、cabozantinib 和 lenvatinib 加 everolimus 最近被批准作为二线治疗药物。本文讨论的新药物增加了可用的治疗选择，并为医生提供了为患者个体化治疗的机会，以期改善疾病控制和生存结果。
