Abstract and Introduction
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.
Renal cell carcinoma (RCC) is among the top 10 most frequently diagnosed cancers worldwide. Approximately 25% of patients with RCC present with metastatic disease at the time of initial diagnosis and require systemic treatment. Moreover, 20–50% of RCC patients with localized disease eventually develop metastatic RCC (mRCC).[1,2]
The advent of immune-checkpoint inhibitors (ICIs) has transformed the treatment landscape of mRCC.[3,4] In recent clinical trials, ICI-based combination therapies have markedly improved survival outcomes in mRCC patients compared with the previous standard of care (sunitinib) in first-line setting.[5–9]
In an era of targeted therapy with antiangiogenic tyrosine kinase inhibitors (TKIs) for mRCC, approximately 52% and 35% of patients reach second- and third-line treatment, respectively. With the introduction of ICI combination therapy, the proportion of patients reaching later lines of treatment is expected to further increase, given the prolonged survival currently obtained.
Physicians are faced with the challenge of choosing an optimal treatment for the individual patient, especially in second and later lines of treatment. The choice of second and subsequent-line TKI or mammalian target of rapamycin (mTOR) inhibitor therapy is a subject of current debate, and data following prior ICI-based therapy is limited. Therefore, this review aims to summarize recent clinical evidence regarding second- and later-line treatment of mRCC.
Curr Opin Urol. 2021;31(3):276-284. © 2021 Wolters Kluwer Health, Inc.