Second- and Later-Line Treatment of Metastatic RCC

What Is Next in Second- and Later-Line Treatment of Metastatic Renal Cell Carcinoma?

Review of the Recent Literature

Keiichiro Mori; Manuela Schmidinger; Fahad Quhal; Shin Egawa; Shahrokh F. Shariat; Viktor Grünwald

Disclosures

Curr Opin Urol. 2021;31(3):276-284. 

In This Article

Abstract and Introduction

Abstract

Purpose of Review: 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.

Recent Findings: 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.

Summary: 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.

Introduction

Renal cell carcinoma (RCC) is among the top 10 most frequently diagnosed cancers worldwide.

Recommendations

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