Hospital Universitario 12 de Octubre, Madrid, Spain.
Royal Free London NHS Fountation Turst, London, UK; UCL DIvision of Surgery and Interventional Science, London, UK.
Eur Urol Oncol. 2019 Sep;2(5):505-514. doi: 10.1016/j.euo.2019.06.022. Epub 2019 Aug 1.
Introduction of additional new agents targeting the vascular endothelial growth factor receptor (VEGFR) and immune checkpoint inhibitors (ICIs) has completely modified the systemic treatment of metastatic renal cell carcinoma (mRCC) during the last years.
A comprehensive (nonsystematic) review to determine the suggested sequence or combinations for the systemic treatment of mRCC.
PubMed and abstracts from main conferences up to December 2018 were reviewed to retrieve the current evidence for treatment of mRCC. Search terms included renal cell carcinoma, systemic therapy, targeted therapy (TT), and immunotherapy.
Marked advances in the treatment of mRCC have been made with novel VEGFR tyrosine kinase inhibitors and multiple ICIs that have been included in the current treatment paradigm of mRCC. Remarkable advance has been made with the combination of double checkpoint blockade. The combination of ipilimumab and nivolumab compared with sunitinib has shown to increase the overall survival in the intermediate- and poor-risk patients based on the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model.
Double checkpoint blockade with ipilimumab and nivolumab has reported overall survival benefit in IMDC intermediate- and poor-risk patients, providing a durable response for a subset of patients. VEGF inhibitors remain the standard of care for favorable-risk patients in the first line. In the immediate future, more consolidated data on combination of VEGF-TT plus ICIs may show similar robust benefit with different safety profiles.
Multiple drugs and sequences are now accepted as effective treatment for metastatic renal cell carcinoma (mRCC). Combination of immune checkpoint inhibitors has shown to increase the overall survival in treatment-naïve mRCC patients. Combinations of immunotherapy and antiangiogenics may be another option in the near future. Outcomes of the first line will determine the sequence, although the best sequence has yet to be defined.
近年来，针对血管内皮生长因子受体（VEGFR）和免疫检查点抑制剂（ICIs）的新型靶向药物的引入，完全改变了转移性肾细胞癌（mRCC）的全身治疗。
对 mRCC 全身治疗的建议顺序或联合治疗进行全面（非系统性）综述。
检索了 2018 年 12 月之前的 PubMed 和主要会议摘要，以获取 mRCC 治疗的最新证据。检索词包括肾细胞癌、全身治疗、靶向治疗（TT）和免疫治疗。
新型 VEGFR 酪氨酸激酶抑制剂和多种 ICIs 的出现，使 mRCC 的治疗取得了显著进展，这些药物已经纳入 mRCC 的当前治疗方案。双重检查点阻断的联合治疗取得了显著进展。与舒尼替尼相比，依匹单抗联合nivolumab 已被证明能增加国际转移性肾细胞癌数据库联盟（IMDC）模型中中危和高危患者的总生存期。
依匹单抗联合 nivolumab 的双重检查点阻断在 IMDC 中危和高危患者中报告了总生存期获益，为一部分患者提供了持久的缓解。VEGF 抑制剂仍然是一线治疗中低危患者的标准治疗方法。在不久的将来，更多关于 VEGF-TT 联合 ICIs 联合治疗的综合数据可能会显示出不同安全性特征的类似强大获益。
现在有多种药物和治疗方案被认为是转移性肾细胞癌（mRCC）的有效治疗方法。免疫检查点抑制剂的联合治疗已被证明能提高初治 mRCC 患者的总生存期。免疫治疗和抗血管生成药物的联合治疗可能是未来的另一种选择。一线治疗的结果将决定治疗顺序，尽管最佳顺序尚未确定。
