Treatment of Advanced Renal Cell Carcinoma: Immunotherapies Have Demonstrated Overall Survival Benefits While Targeted Therapies Have Not

CONTEXT: Current guidelines suggest several targeted therapies (TTs) and immunotherapies (ITs) in the treatment of advanced or metastatic renal cell carcinoma (mRCC). Ideal sequencing of these treatments is unclear. OBJECTIVE: The primary objective was to evaluate the overall survival (OS) data of t...

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Autores principales: Hemminki, Otto, Perlis, Nathan, Bjorklund, Johan, Finelli, Antonio, Zlotta, Alexandre R., Hemminki, Akseli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317793/
https://www.ncbi.nlm.nih.gov/pubmed/34337479
http://dx.doi.org/10.1016/j.euros.2020.11.003
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author Hemminki, Otto
Perlis, Nathan
Bjorklund, Johan
Finelli, Antonio
Zlotta, Alexandre R.
Hemminki, Akseli
author_facet Hemminki, Otto
Perlis, Nathan
Bjorklund, Johan
Finelli, Antonio
Zlotta, Alexandre R.
Hemminki, Akseli
author_sort Hemminki, Otto
collection PubMed
description CONTEXT: Current guidelines suggest several targeted therapies (TTs) and immunotherapies (ITs) in the treatment of advanced or metastatic renal cell carcinoma (mRCC). Ideal sequencing of these treatments is unclear. OBJECTIVE: The primary objective was to evaluate the overall survival (OS) data of the treatments approved for mRCC. Secondary objectives included evaluating other signs of efficacy and adverse events. EVIDENCE ACQUISITION: We reviewed the current Food and Drug Administration–approved treatments for mRCC. Trials associated with approval were reviewed. We also included pre- and postapproval publications when appropriate. EVIDENCE SYNTHESIS: There is minimal evidence supporting OS benefit for the nine approved TTs. They result in adverse events and are a considerable economic burden. For these reasons, their future role in mRCC treatment should be re-evaluated, given the emergence of IT that have demonstrated OS benefits. Accumulating long-term survival data with high-dose interleukin-2 treatment suggests that this older treatment could still be considered for eligible patients. Checkpoint inhibitors have shown promising OS and durable responses; as such, the high cost of treatment might be justified. However, the available evidence does not suggest that adding TT to IT would increase efficacy over IT alone, but would add toxicity. CONCLUSIONS: Trial data supporting OS benefit are much stronger for ITs than for TTs. Combining checkpoint inhibitors with TTs has not been shown to produce better OS than checkpoint inhibitors alone, while more adverse events are present. Granting drug approvals based on efficacy without demonstrated OS benefit should be revisited. PATIENT SUMMARY: Approved treatments for metastatic kidney cancer include targeted and immune-based therapies. The former commonly produces temporary tumour shrinkage, but survival benefits are unclear. All approved immunotherapies have increased survival, and a proportion of patients appear cured.
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spelling pubmed-83177932021-07-29 Treatment of Advanced Renal Cell Carcinoma: Immunotherapies Have Demonstrated Overall Survival Benefits While Targeted Therapies Have Not Hemminki, Otto Perlis, Nathan Bjorklund, Johan Finelli, Antonio Zlotta, Alexandre R. Hemminki, Akseli Eur Urol Open Sci Review – Kidney Cancer CONTEXT: Current guidelines suggest several targeted therapies (TTs) and immunotherapies (ITs) in the treatment of advanced or metastatic renal cell carcinoma (mRCC). Ideal sequencing of these treatments is unclear. OBJECTIVE: The primary objective was to evaluate the overall survival (OS) data of the treatments approved for mRCC. Secondary objectives included evaluating other signs of efficacy and adverse events. EVIDENCE ACQUISITION: We reviewed the current Food and Drug Administration–approved treatments for mRCC. Trials associated with approval were reviewed. We also included pre- and postapproval publications when appropriate. EVIDENCE SYNTHESIS: There is minimal evidence supporting OS benefit for the nine approved TTs. They result in adverse events and are a considerable economic burden. For these reasons, their future role in mRCC treatment should be re-evaluated, given the emergence of IT that have demonstrated OS benefits. Accumulating long-term survival data with high-dose interleukin-2 treatment suggests that this older treatment could still be considered for eligible patients. Checkpoint inhibitors have shown promising OS and durable responses; as such, the high cost of treatment might be justified. However, the available evidence does not suggest that adding TT to IT would increase efficacy over IT alone, but would add toxicity. CONCLUSIONS: Trial data supporting OS benefit are much stronger for ITs than for TTs. Combining checkpoint inhibitors with TTs has not been shown to produce better OS than checkpoint inhibitors alone, while more adverse events are present. Granting drug approvals based on efficacy without demonstrated OS benefit should be revisited. PATIENT SUMMARY: Approved treatments for metastatic kidney cancer include targeted and immune-based therapies. The former commonly produces temporary tumour shrinkage, but survival benefits are unclear. All approved immunotherapies have increased survival, and a proportion of patients appear cured. Elsevier 2020-11-28 /pmc/articles/PMC8317793/ /pubmed/34337479 http://dx.doi.org/10.1016/j.euros.2020.11.003 Text en © 2020 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review – Kidney Cancer
Hemminki, Otto
Perlis, Nathan
Bjorklund, Johan
Finelli, Antonio
Zlotta, Alexandre R.
Hemminki, Akseli
Treatment of Advanced Renal Cell Carcinoma: Immunotherapies Have Demonstrated Overall Survival Benefits While Targeted Therapies Have Not
title Treatment of Advanced Renal Cell Carcinoma: Immunotherapies Have Demonstrated Overall Survival Benefits While Targeted Therapies Have Not
title_full Treatment of Advanced Renal Cell Carcinoma: Immunotherapies Have Demonstrated Overall Survival Benefits While Targeted Therapies Have Not
title_fullStr Treatment of Advanced Renal Cell Carcinoma: Immunotherapies Have Demonstrated Overall Survival Benefits While Targeted Therapies Have Not
title_full_unstemmed Treatment of Advanced Renal Cell Carcinoma: Immunotherapies Have Demonstrated Overall Survival Benefits While Targeted Therapies Have Not
title_short Treatment of Advanced Renal Cell Carcinoma: Immunotherapies Have Demonstrated Overall Survival Benefits While Targeted Therapies Have Not
title_sort treatment of advanced renal cell carcinoma: immunotherapies have demonstrated overall survival benefits while targeted therapies have not
topic Review – Kidney Cancer
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317793/
https://www.ncbi.nlm.nih.gov/pubmed/34337479
http://dx.doi.org/10.1016/j.euros.2020.11.003
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