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Combination of immune checkpoint inhibitors and tyrosine kinase inhibitors for the treatment of renal cell carcinoma

Stühler V, Rausch S, Maas JM, Stenzl A, Bedke J

Expert opinion on biological therapy, 2021

Abstract

INTRODUCTION: We have experienced several paradigm shifts and substantial changes in the treatment of metastatic renal cell carcinoma (mRCC) over the last two decades. Combination therapy with immune checkpoint inhibitors (ICI) as a dual combination (ICI-ICI) or with VEGFR-tyrosine kinase inhibitors (VEGF-TKI) has shown remarkable efficacy in mRCC patients and has become the standard of care in first-line therapy.

AREAS COVERED: In this review, we will discuss the background as well as the benefits of combining ICI with TKI compared to ICI-ICI combination therapy for mRCC treatment and will also briefly highlight biomarkers for patient selection on therapies to improve patient outcomes and limit toxicities.

EXPERT OPINION: Due to the mediated additional anti-tumor effects, there is a strong rationale to combine ICIs and TKIs for mRCC therapy. When comparing first-line therapy options, the exceptionally higher ORR and PFS for the ICI-TKI combinations should be highlighted, whereas, nevertheless, the complete response rate is slightly higher for the ICI-ICI combination. In terms of an individualized therapeutic approach, biomarkers predicting the success or failure of an anti-VEGF-based regimen or ICI therapy as a corresponding mono - or combination therapy are lacking so far, however, gene expression signatures can be a landmark in this field.

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