What is next in second- and later-line treatment of metastatic renal cell carcinoma? review of the recent literature.

Abstract

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.