Abstract：
Immunotherapy (IO) with checkpoint inhibitors with or without anti-angiogenic tyrosine kinase inhibitor (TKI)-based combinations have demonstrated superior efficacy over sunitinib for treatment-naive patients with metastatic clear-cell renal cell carcinoma (mRCC). Four of these combinations (nivolumab plus ipilimumab, pembrolizumab plus axitinib, nivolumab plus cabozantinib and pembrolizumab plus lenvatinib) represent new front-line standard-of-care options for mRCC patients, according to the International Metastatic RCC Database Consortium (IMDC) subgroups. Questions over the optimal treatment between IO-IO or IO-TKI combinations for mRCC patients in intermediate/poor IMDC risk groups and the optimal IO-TKI regimen for all IMDC risk groups remain unanswered. This review will focus on the biological pathways that have driven the hypothesis of a synergistic combination of such agents and their efficacy results, with consideration of response and survival outcomes in the overall population of phase three pivotal trials as well as in specific subgroups of interest.
摘要：
具有或不具有基于抗血管生成酪氨酸激酶抑制剂(TKI)的组合的检查点抑制剂的免疫疗法(IO)对于患有转移性透明细胞肾细胞癌(mRCC)的未经治疗的患者已证明优于舒尼替尼的疗效。其中四种组合(nivolumab+ipilimumab，派博利珠单抗加阿西替尼，nivolumab+cabozantinib和pembrolizumab+lenvatinib)代表mRCC患者新的一线标准治疗选择，根据国际转移性RCC数据库联盟（IMDC）亚组。对于中等/较差IMDC风险组的mRCC患者，IO-IO或IO-TKI组合之间的最佳治疗以及所有IMDC风险组的最佳IO-TKI方案的问题仍未得到解答。这篇综述将集中在驱动这种药物的协同组合的假设的生物学途径及其疗效结果。同时考虑到3期关键试验的总体人群以及感兴趣的特定亚组的应答和生存结局.
