转化为简体中文并保持原来的句子结构： 转移性肾癌的一线治疗可以分为三个主要阶段。 2006年，酪氨酸激酶抑制剂问世，细胞因子时代被取代。 直到2018年，标准的一线治疗是使用舒尼替尼或帕博西尼。 在过去的十年中，已经尝试了许多结合这些已获批准或正在开发的药物的尝试，但主要是由于无法忍受的毒性而没有成功。 在2018年，我们在转移性肾肿瘤的治疗中达到了一个新阶段。 今年，ipilimumab和nivolumab的联合免疫疗法获得了批准。 从那时起，免疫疗法和靶向治疗的联合治疗导致了成功。 我们总结的主要目标是按时间顺序呈现在欧洲已经获得批准的联合治疗的临床试验，以及最新的III期临床试验。 还旨在提供一个简要实用的指南，以便根据这些试验的结果来决定一线治疗。

First-line treatment of metastatic renal cancer can be divided into three main phases. The cytokine era was replaced by targeted therapies in 2006 with the introduction of tyrosine kinase inhibitors. Until 2018, the standard first-line therapy was the use of sunitinib or pazopanib. Over the past decade, numerous attempts have been made to combine these drugs, which are already approved or in development, but these attempts have not been successful, primarily because of intolerable toxicity. In 2018, we reached a new stage in the treatment of metastatic renal tumors. This year, the combination immunotherapy of ipilimumab and nivolumab was approved. Since then, the combination of immunotherapy and targeted therapies has led to success. The main objective of our summary is to present in chronological order the clinical trials of combination therapies already approved in Europe, as well as the most recent phase III clinical trials. It is also intended to provide a brief practical guide on how to decide on first-line therapy based on the results of these trials.