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A model‐based meta‐analysis of immune‐related adverse events during immune checkpoint inhibitors treatment for NSCLC

Immune checkpoint inhibitors (ICIs) have become a vital part of the therapeutic landscape for non‐small cell lung cancer (NSCLC) in recent years benefiting from their remarkable efficacy. However, ICIs are associated with potentially life‐threatening immune‐related adverse events (irAEs). This study...

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Autores principales: Zhang, Renwei, Kong, Daming, Chen, Rong, Guo, Yuchen, Jian, Weizhe, Han, Mengyi, Zhou, Tianyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381889/
https://www.ncbi.nlm.nih.gov/pubmed/35763678
http://dx.doi.org/10.1002/psp4.12834
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author Zhang, Renwei
Kong, Daming
Chen, Rong
Guo, Yuchen
Jian, Weizhe
Han, Mengyi
Zhou, Tianyan
author_facet Zhang, Renwei
Kong, Daming
Chen, Rong
Guo, Yuchen
Jian, Weizhe
Han, Mengyi
Zhou, Tianyan
author_sort Zhang, Renwei
collection PubMed
description Immune checkpoint inhibitors (ICIs) have become a vital part of the therapeutic landscape for non‐small cell lung cancer (NSCLC) in recent years benefiting from their remarkable efficacy. However, ICIs are associated with potentially life‐threatening immune‐related adverse events (irAEs). This study aims to quantify dose dependence and additional influencing factors of both any grade and grade greater than or equal to 3 irAEs in patients with NSCLC treated by ICIs. The trial‐level irAE data was collected and pooled from 129 cohorts in 81 clinical studies. A logit‐transformed meta‐regression model was applied to derive the quantitative relationship of irAE rate and ICI exposure. Programmed cell death‐1 (PD‐1) or programmed cell death ligand‐1 (PD‐L1) inhibitors showed no dose dependence in patients with NSCLC, whereas cytotoxic T lymphocyte–associated antigen 4 (CTLA‐4) inhibitors exhibited a statistically significant dose dependence when used alone or combined with PD‐1 or PD‐L1 inhibitors. Besides, therapy line and combination of ICIs with chemotherapy or target therapy were significant covariates. Hopefully, the results of this study can improve clinicians’ awareness of irAEs and be helpful for clinical decisions during ICI treatment for NSCLC.
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spelling pubmed-93818892022-08-19 A model‐based meta‐analysis of immune‐related adverse events during immune checkpoint inhibitors treatment for NSCLC Zhang, Renwei Kong, Daming Chen, Rong Guo, Yuchen Jian, Weizhe Han, Mengyi Zhou, Tianyan CPT Pharmacometrics Syst Pharmacol Research Immune checkpoint inhibitors (ICIs) have become a vital part of the therapeutic landscape for non‐small cell lung cancer (NSCLC) in recent years benefiting from their remarkable efficacy. However, ICIs are associated with potentially life‐threatening immune‐related adverse events (irAEs). This study aims to quantify dose dependence and additional influencing factors of both any grade and grade greater than or equal to 3 irAEs in patients with NSCLC treated by ICIs. The trial‐level irAE data was collected and pooled from 129 cohorts in 81 clinical studies. A logit‐transformed meta‐regression model was applied to derive the quantitative relationship of irAE rate and ICI exposure. Programmed cell death‐1 (PD‐1) or programmed cell death ligand‐1 (PD‐L1) inhibitors showed no dose dependence in patients with NSCLC, whereas cytotoxic T lymphocyte–associated antigen 4 (CTLA‐4) inhibitors exhibited a statistically significant dose dependence when used alone or combined with PD‐1 or PD‐L1 inhibitors. Besides, therapy line and combination of ICIs with chemotherapy or target therapy were significant covariates. Hopefully, the results of this study can improve clinicians’ awareness of irAEs and be helpful for clinical decisions during ICI treatment for NSCLC. John Wiley and Sons Inc. 2022-07-04 2022-08 /pmc/articles/PMC9381889/ /pubmed/35763678 http://dx.doi.org/10.1002/psp4.12834 Text en © 2022 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research
Zhang, Renwei
Kong, Daming
Chen, Rong
Guo, Yuchen
Jian, Weizhe
Han, Mengyi
Zhou, Tianyan
A model‐based meta‐analysis of immune‐related adverse events during immune checkpoint inhibitors treatment for NSCLC
title A model‐based meta‐analysis of immune‐related adverse events during immune checkpoint inhibitors treatment for NSCLC
title_full A model‐based meta‐analysis of immune‐related adverse events during immune checkpoint inhibitors treatment for NSCLC
title_fullStr A model‐based meta‐analysis of immune‐related adverse events during immune checkpoint inhibitors treatment for NSCLC
title_full_unstemmed A model‐based meta‐analysis of immune‐related adverse events during immune checkpoint inhibitors treatment for NSCLC
title_short A model‐based meta‐analysis of immune‐related adverse events during immune checkpoint inhibitors treatment for NSCLC
title_sort model‐based meta‐analysis of immune‐related adverse events during immune checkpoint inhibitors treatment for nsclc
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381889/
https://www.ncbi.nlm.nih.gov/pubmed/35763678
http://dx.doi.org/10.1002/psp4.12834
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