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Treatment of Refractory Metastatic Renal Cell Carcinoma

SIMPLE SUMMARY: The treatment of metastatic renal cell carcinoma continues to rapidly evolve, with various combinations of immune checkpoint inhibitors and targeted tyrosine kinase inhibitors improving outcomes in the first-line setting. However, a significant subset of patients fail to respond to t...

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Autores principales: Vento, Joseph A., Rini, Brian I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599552/
https://www.ncbi.nlm.nih.gov/pubmed/36291789
http://dx.doi.org/10.3390/cancers14205005
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author Vento, Joseph A.
Rini, Brian I.
author_facet Vento, Joseph A.
Rini, Brian I.
author_sort Vento, Joseph A.
collection PubMed
description SIMPLE SUMMARY: The treatment of metastatic renal cell carcinoma continues to rapidly evolve, with various combinations of immune checkpoint inhibitors and targeted tyrosine kinase inhibitors improving outcomes in the first-line setting. However, a significant subset of patients fail to respond to these therapies, and many patients eventually progress, necessitating effective therapeutic options in the treatment-refractory setting. Here, we review the treatment of refractory renal cell carcinoma, including the current standard of care, ongoing trials with the potential to alter current paradigms, and considerations for non-clear cell histologies. ABSTRACT: First-line treatment for metastatic renal cell carcinoma (mRCC) rapidly shifted in recent years with the advent of combination therapies, including immune checkpoint inhibitor (ICI) doublets and combinations of an ICI with a vascular endothelial growth factor receptor (VEGFR) targeted tyrosine kinase inhibitor (TKI). Despite improvements in overall survival and many durable responses, there exists a significant number of patients who fail to respond to these agents, and many patients eventually progress. Given the rapid changes in the front-line setting, it is essential to understand treatment options in refractory mRCC. Here, we review the evidence behind current options for later-line therapies, often involving additional VEGFR-TKIs alone or in combination with mammalian target of rapamycin (mTOR) targeted agents, as well as situations where consideration of immunotherapy rechallenge may be appropriate. Additionally, we describe ongoing clinical trials examining concurrent ICI and TKI in the refractory setting, as well as those studying novel agents, such as targeted drug–antibody conjugates and hypoxia inducible factor 2α (HIF-2α) inhibitors. Finally, we review considerations for non-clear cell histologies in the refractory setting and mechanisms of resistance in mRCC.
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spelling pubmed-95995522022-10-27 Treatment of Refractory Metastatic Renal Cell Carcinoma Vento, Joseph A. Rini, Brian I. Cancers (Basel) Review SIMPLE SUMMARY: The treatment of metastatic renal cell carcinoma continues to rapidly evolve, with various combinations of immune checkpoint inhibitors and targeted tyrosine kinase inhibitors improving outcomes in the first-line setting. However, a significant subset of patients fail to respond to these therapies, and many patients eventually progress, necessitating effective therapeutic options in the treatment-refractory setting. Here, we review the treatment of refractory renal cell carcinoma, including the current standard of care, ongoing trials with the potential to alter current paradigms, and considerations for non-clear cell histologies. ABSTRACT: First-line treatment for metastatic renal cell carcinoma (mRCC) rapidly shifted in recent years with the advent of combination therapies, including immune checkpoint inhibitor (ICI) doublets and combinations of an ICI with a vascular endothelial growth factor receptor (VEGFR) targeted tyrosine kinase inhibitor (TKI). Despite improvements in overall survival and many durable responses, there exists a significant number of patients who fail to respond to these agents, and many patients eventually progress. Given the rapid changes in the front-line setting, it is essential to understand treatment options in refractory mRCC. Here, we review the evidence behind current options for later-line therapies, often involving additional VEGFR-TKIs alone or in combination with mammalian target of rapamycin (mTOR) targeted agents, as well as situations where consideration of immunotherapy rechallenge may be appropriate. Additionally, we describe ongoing clinical trials examining concurrent ICI and TKI in the refractory setting, as well as those studying novel agents, such as targeted drug–antibody conjugates and hypoxia inducible factor 2α (HIF-2α) inhibitors. Finally, we review considerations for non-clear cell histologies in the refractory setting and mechanisms of resistance in mRCC. MDPI 2022-10-13 /pmc/articles/PMC9599552/ /pubmed/36291789 http://dx.doi.org/10.3390/cancers14205005 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Vento, Joseph A.
Rini, Brian I.
Treatment of Refractory Metastatic Renal Cell Carcinoma
title Treatment of Refractory Metastatic Renal Cell Carcinoma
title_full Treatment of Refractory Metastatic Renal Cell Carcinoma
title_fullStr Treatment of Refractory Metastatic Renal Cell Carcinoma
title_full_unstemmed Treatment of Refractory Metastatic Renal Cell Carcinoma
title_short Treatment of Refractory Metastatic Renal Cell Carcinoma
title_sort treatment of refractory metastatic renal cell carcinoma
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599552/
https://www.ncbi.nlm.nih.gov/pubmed/36291789
http://dx.doi.org/10.3390/cancers14205005
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