Zibelman Matthew, Plimack Elizabeth R
From Department of Hematology/Oncology, Fox Chase Cancer Center, and Temple Health, Philadelphia, Pennsylvania.
J Natl Compr Canc Netw. 2017 Jun;15(6):841-847. doi: 10.6004/jnccn.2017.0103.
Before 2005, systemic treatment of metastatic renal cell carcinoma (RCC) was limited to a few minimally effective options. Since then, new agents have emerged targeting the vascular endothelial growth factor and mTOR pathways, which has improved outcomes for patients. Options increased even further beginning in 2015 with 3 new agents, including the addition of nivolumab, the first immune checkpoint inhibitor to demonstrate improved survival in RCC. RCC has long been considered a malignancy with immunogenic potential, and nivolumab offers the potential for durable responses in some patients with a generally tolerable toxicity profile. With so many drugs available to clinicians and patients, properly integrating immune checkpoint blockade (ICB) into the treatment paradigm is challenging. Additionally, emerging research with other ICB agents, as well as ongoing trials of combination strategies, is likely to further impact clinical decision-making. This article attempts to provide some context to inform systemic treatment decisions in the current landscape, with a particular emphasis on the role of immunotherapy, outlines the ongoing immunotherapy research in RCC, and discusses how treatment may evolve.
2005年之前,转移性肾细胞癌(RCC)的全身治疗仅限于少数几种疗效甚微的选择。从那时起,出现了针对血管内皮生长因子和mTOR通路的新型药物,改善了患者的治疗效果。从2015年开始,选择进一步增加,有3种新型药物,包括纳武单抗的加入,它是首个在RCC中显示能提高生存率的免疫检查点抑制剂。RCC长期以来一直被认为是具有免疫原性潜力的恶性肿瘤,纳武单抗在一些患者中具有产生持久反应的潜力,且毒性特征总体上可以耐受。有如此多的药物可供临床医生和患者使用,将免疫检查点阻断(ICB)合理纳入治疗模式具有挑战性。此外,其他ICB药物的新研究以及联合策略的正在进行的试验,可能会进一步影响临床决策。本文试图提供一些背景信息,为当前形势下的全身治疗决策提供参考,特别强调免疫治疗的作用,概述RCC正在进行的免疫治疗研究,并讨论治疗可能如何演变。