Zahoor Haris, Rini Brian I
a Taussig Cancer Institute , Cleveland Clinic , Cleveland , OH , USA.
Expert Opin Emerg Drugs. 2016 Dec;21(4):431-440. doi: 10.1080/14728214.2016.1244263. Epub 2016 Oct 12.
The landscape of systemic treatment for metastatic renal cell carcinoma (RCC) has dramatically changed with the introduction of targeted agents including vascular endothelial growth factor (VEGF) inhibitors. Recently, multiple new agents including growth factor receptor antagonists and a checkpoint inhibitor were approved for the treatment of refractory metastatic RCC based on encouraging benefit shown in clinical trials. Areas covered: The background and biological rationale of existing treatment options including a brief discussion of clinical trials which led to their approval, is presented. This is followed by reviewing the limitations of these therapeutic options, medical need to develop new treatments and major goals of ongoing research. We then discuss two recently approved growth factor receptor antagonists i.e. cabozantinib and lenvatinib, and a recently approved checkpoint inhibitor, nivolumab, and issues pertaining to drug development, and future directions in treatment of metastatic RCC. Expert opinion: Recently approved growth factor receptor antagonists have shown encouraging survival benefit but associated drug toxicity is a major issue. Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, has similarly shown survival benefit and is well tolerated. With multiple options now available in this patient population, the right sequence of these agents remains to be determined.
随着包括血管内皮生长因子（VEGF）抑制剂在内的靶向药物的引入，转移性肾细胞癌（RCC）的全身治疗格局发生了巨大变化。最近，基于临床试验中显示的令人鼓舞的疗效，包括生长因子受体拮抗剂和一种检查点抑制剂在内的多种新型药物被批准用于治疗难治性转移性RCC。涵盖领域：介绍了现有治疗方案的背景和生物学原理，包括对导致其获批的临床试验的简要讨论。随后回顾了这些治疗方案的局限性、开发新治疗方法的医学需求以及正在进行的研究的主要目标。然后我们讨论了两种最近获批的生长因子受体拮抗剂，即卡博替尼和乐伐替尼，以及一种最近获批的检查点抑制剂纳武单抗，以及与药物开发相关的问题和转移性RCC治疗的未来方向。专家观点：最近获批的生长因子受体拮抗剂已显示出令人鼓舞的生存获益，但相关的药物毒性是一个主要问题。纳武单抗，一种程序性死亡1（PD-1）检查点抑制剂，同样显示出生存获益且耐受性良好。在这一患者群体中现在有多种选择，这些药物的正确使用顺序仍有待确定。
