Department of Urology, Medical University of Vienna, Vienna, Austria.
Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
Curr Opin Urol. 2021 May 1;31(3):276-284. doi: 10.1097/MOU.0000000000000867.
The current treatment landscape of metastatic renal cell carcinoma has changed dramatically from the dominance of single-agent tyrosine kinase inhibitor (TKI) therapy to immune-checkpoint inhibitor (ICI)-based combinations in recent years. However, the optimal subsequent therapy remains ill-defined owing to the novelty of this approach.
Treatment with TKIs after failure of single or dual ICI therapies may result in robust clinical efficacy. Nonetheless, there is a trend toward lower efficacy of TKIs after previous ICI-TKI combination therapy. Currently, tivozanib is the only drug whose third- and later-line use after failure of TKI and ICI is supported by evidence, with significantly longer progression-free survival and higher objective response rates than sorafenib. Data from retrospective studies highlight the safety and clinical activity of ICI rechallenge.
Overall, the level of evidence remains low. Treatment after failure of dual ICI therapy is not well defined and may consist of any available TKI. Although first-line use of TKI is less common, strong evidence suggests cabozantinib or nivolumab as standard options in that setting. The recommendations after first-line TKI-ICI therapy failure mirror this recommendation, although the data are less robust.
综述目的：近年来，转移性肾细胞癌的治疗格局发生了巨大变化，从单一药物酪氨酸激酶抑制剂（TKI）治疗为主，转变为免疫检查点抑制剂（ICI）为基础的联合治疗。然而，由于这种方法具有新颖性，最佳的后续治疗方法仍不明确。
最新发现：ICI 单一或双重治疗失败后使用 TKI 治疗可能会产生显著的临床疗效。然而，与先前接受 ICI-TKI 联合治疗相比，TKI 治疗后的疗效呈下降趋势。目前，替沃扎尼布是唯一一种在 TKI 和 ICI 治疗失败后，有证据支持其在三线及以后使用的药物，其无进展生存期和客观缓解率均显著高于索拉非尼。来自回顾性研究的数据强调了ICI 再挑战的安全性和临床活性。
总结：总体而言，证据水平仍然较低。双重 ICI 治疗失败后的治疗方法尚不清楚，可能包括任何可用的 TKI。尽管 TKI 的一线使用不太常见，但有强有力的证据表明卡博替尼或纳武利尤单抗是该治疗方案的标准选择。一线 TKI-ICI 治疗失败后的建议反映了这一建议，尽管数据不太可靠。
