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Treatment-Related Adverse Events of Combination Immune Checkpoint Inhibitors: Systematic Review and Meta-Analysis

Background: Although clinical practice guidelines for the management of Immune Checkpoint Inhibitor (ICI)-related adverse events have recently been published, precise and nuanced toxicity data for combination ICI therapy are lacking. Therefore, herein we have conducted a systematic review and meta-a...

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Autores principales: Park, Robin, Lopes, Laercio, Cristancho, Cagney R., Riano, Ivy M., Saeed, Anwaar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090167/
https://www.ncbi.nlm.nih.gov/pubmed/32257944
http://dx.doi.org/10.3389/fonc.2020.00258
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author Park, Robin
Lopes, Laercio
Cristancho, Cagney R.
Riano, Ivy M.
Saeed, Anwaar
author_facet Park, Robin
Lopes, Laercio
Cristancho, Cagney R.
Riano, Ivy M.
Saeed, Anwaar
author_sort Park, Robin
collection PubMed
description Background: Although clinical practice guidelines for the management of Immune Checkpoint Inhibitor (ICI)-related adverse events have recently been published, precise and nuanced toxicity data for combination ICI therapy are lacking. Therefore, herein we have conducted a systematic review and meta-analysis of published clinical trials on combination ICI to synthesize the treatment-related adverse event (TRAE) profile of combination ICI therapy. Methods: PUBMED, EMBASE, and the Cochrane Database/EBM were searched for eligible studies. Clinical trials evaluating combination immune checkpoint inhibitor therapy in advanced unresectable cancer were included in the analysis based on prespecified criteria. Risk of bias across studies was evaluated using Begg's funnel plot and Egger's regression test. The summary outcomes were pooled risk ratios (RR) and the logit-transformed proportion for incidence data. Results: A total of 18 studies comprising 2,767 patients across 10 cancer types were included in the final analysis. Combination ICI was associated with a slightly higher risk of all-grade adverse events (RR 1.07 [95% CI 1.03–1.11]) and markedly greater risk of grade 3 or higher adverse events (RR 2.21 [95% CI 1.57–3.10]) compared to monotherapy ICI. Subgroup analyses showed significant differences in risk of grade 3 or higher adverse events between treatment types (PD-1 + CTLA-4 and PD-L1 + CTLA-4), among cancer types, and among dosing regimens (N1I3, N3I1, and D20T1). The incidence of all-grade adverse events was 0.905 [95% CI 0.842–0.945], and the ratio of grade 3 or higher events to all-grade adverse events was 0.396 [95% CI 0.315–0.483]. The most common all-grade TRAEs were diarrhea/colitis, fatigue/asthenia, nausea/vomiting, rash, and pruritis. Conclusion: Combination ICI therapy has a significantly different treatment-related adverse event profile compared to monotherapy.
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spelling pubmed-70901672020-03-31 Treatment-Related Adverse Events of Combination Immune Checkpoint Inhibitors: Systematic Review and Meta-Analysis Park, Robin Lopes, Laercio Cristancho, Cagney R. Riano, Ivy M. Saeed, Anwaar Front Oncol Oncology Background: Although clinical practice guidelines for the management of Immune Checkpoint Inhibitor (ICI)-related adverse events have recently been published, precise and nuanced toxicity data for combination ICI therapy are lacking. Therefore, herein we have conducted a systematic review and meta-analysis of published clinical trials on combination ICI to synthesize the treatment-related adverse event (TRAE) profile of combination ICI therapy. Methods: PUBMED, EMBASE, and the Cochrane Database/EBM were searched for eligible studies. Clinical trials evaluating combination immune checkpoint inhibitor therapy in advanced unresectable cancer were included in the analysis based on prespecified criteria. Risk of bias across studies was evaluated using Begg's funnel plot and Egger's regression test. The summary outcomes were pooled risk ratios (RR) and the logit-transformed proportion for incidence data. Results: A total of 18 studies comprising 2,767 patients across 10 cancer types were included in the final analysis. Combination ICI was associated with a slightly higher risk of all-grade adverse events (RR 1.07 [95% CI 1.03–1.11]) and markedly greater risk of grade 3 or higher adverse events (RR 2.21 [95% CI 1.57–3.10]) compared to monotherapy ICI. Subgroup analyses showed significant differences in risk of grade 3 or higher adverse events between treatment types (PD-1 + CTLA-4 and PD-L1 + CTLA-4), among cancer types, and among dosing regimens (N1I3, N3I1, and D20T1). The incidence of all-grade adverse events was 0.905 [95% CI 0.842–0.945], and the ratio of grade 3 or higher events to all-grade adverse events was 0.396 [95% CI 0.315–0.483]. The most common all-grade TRAEs were diarrhea/colitis, fatigue/asthenia, nausea/vomiting, rash, and pruritis. Conclusion: Combination ICI therapy has a significantly different treatment-related adverse event profile compared to monotherapy. Frontiers Media S.A. 2020-03-17 /pmc/articles/PMC7090167/ /pubmed/32257944 http://dx.doi.org/10.3389/fonc.2020.00258 Text en Copyright © 2020 Park, Lopes, Cristancho, Riano and Saeed. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Park, Robin
Lopes, Laercio
Cristancho, Cagney R.
Riano, Ivy M.
Saeed, Anwaar
Treatment-Related Adverse Events of Combination Immune Checkpoint Inhibitors: Systematic Review and Meta-Analysis
title Treatment-Related Adverse Events of Combination Immune Checkpoint Inhibitors: Systematic Review and Meta-Analysis
title_full Treatment-Related Adverse Events of Combination Immune Checkpoint Inhibitors: Systematic Review and Meta-Analysis
title_fullStr Treatment-Related Adverse Events of Combination Immune Checkpoint Inhibitors: Systematic Review and Meta-Analysis
title_full_unstemmed Treatment-Related Adverse Events of Combination Immune Checkpoint Inhibitors: Systematic Review and Meta-Analysis
title_short Treatment-Related Adverse Events of Combination Immune Checkpoint Inhibitors: Systematic Review and Meta-Analysis
title_sort treatment-related adverse events of combination immune checkpoint inhibitors: systematic review and meta-analysis
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090167/
https://www.ncbi.nlm.nih.gov/pubmed/32257944
http://dx.doi.org/10.3389/fonc.2020.00258
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