A Network Comparison on Safety Profiling of Immune Checkpoint Inhibitors in Advanced Lung Cancer

BackgroundImmune checkpoint inhibitors (ICIs) have become one of the standard treatment options for advanced lung cancer. However, adverse events (AEs), particularly immune–related AEs (irAEs), caused by these drugs have aroused public attention. The current network meta-analysis (NMA) aimed to comp...

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Autores principales:	Yi-Dan Yan, Jiu-Jie Cui, Jie Fu, Ying-Jie Su, Xiao-Yu Chen, Zhi-Chun Gu, Hou-Wen Lin
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	immune checkpoint inhibitors safety lung cancer adverse events network comparison Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/9b59e787eb32462b809902f07e7fe08a
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spelling	oai:doaj.org-article:9b59e787eb32462b809902f07e7fe08a2021-12-03T04:44:53ZA Network Comparison on Safety Profiling of Immune Checkpoint Inhibitors in Advanced Lung Cancer1664-322410.3389/fimmu.2021.760737https://doaj.org/article/9b59e787eb32462b809902f07e7fe08a2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.760737/fullhttps://doaj.org/toc/1664-3224BackgroundImmune checkpoint inhibitors (ICIs) have become one of the standard treatment options for advanced lung cancer. However, adverse events (AEs), particularly immune–related AEs (irAEs), caused by these drugs have aroused public attention. The current network meta-analysis (NMA) aimed to compare the risk of AEs across different ICI–based regimens in patients with advanced lung cancer.MethodsWe systematically searched the PubMed, EMBASE, and Cochrane Library databases (from inception to 19 April 2021) for relevant randomized controlled trials (RCTs) that compared two or more treatments, with at least one ICI administered to patients with advanced lung cancer. The primary outcomes were treatment–related AEs and irAEs, including grade 1–5 and grade 3–5. The secondary outcomes were grade 1–5 and grade 3–5 irAEs in specific organs. Both pairwise and network meta-analyses were conducted for chemotherapy, ICI monotherapy, ICI monotherapy + chemotherapy, dual ICIs therapy, and dual ICIs + chemotherapy for all safety outcomes. Node–splitting analyses were performed to test inconsistencies in network. Sensitivity analyses were adopted by restricting phase III RCTs and studies that enrolled patients with non–small cell lung cancer.ResultsOverall, 38 RCTs involving 22,178 patients with advanced lung cancer were enrolled. Both pooled incidence and NMA indicated that treatments containing chemotherapy increased the risk of treatment–related AEs when compared with ICI-based regimens without chemotherapy. As for grade 1–5 irAEs, dual ICIs + chemotherapy was associated with the highest risk of irAEs (probability in ranking first: 50.5%), followed by dual-ICI therapy (probability in ranking second: 47.2%), ICI monotherapy (probability in ranking third: 80.0%), ICI monotherapy + chemotherapy (probability in ranking fourth: 98.0%), and finally chemotherapy (probability in ranking fifth: 100.0%). In grade 3–5 irAEs, subtle differences were observed; when ranked from least safe to safest, the trend was dual ICIs therapy (60.4%), dual ICIs + chemotherapy (42.5%), ICI monotherapy (76.3%), ICI monotherapy + chemotherapy (95.0%), and chemotherapy (100.0%). Furthermore, detailed comparisons between ICI–based options provided irAE profiles based on specific organ/system and severity.ConclusionsIn consideration of overall immune–related safety profiles, ICI monotherapy + chemotherapy might be a better choice among ICI–based treatments for advanced lung cancer. The safety profiles of ICI–based treatments are various by specific irAEs and their severity.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42021268650Yi-Dan YanJiu-Jie CuiJie FuYing-Jie SuXiao-Yu ChenZhi-Chun GuHou-Wen LinFrontiers Media S.A.articleimmune checkpoint inhibitorssafetylung canceradverse eventsnetwork comparisonImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	immune checkpoint inhibitors safety lung cancer adverse events network comparison Immunologic diseases. Allergy RC581-607
spellingShingle	immune checkpoint inhibitors safety lung cancer adverse events network comparison Immunologic diseases. Allergy RC581-607 Yi-Dan Yan Jiu-Jie Cui Jie Fu Ying-Jie Su Xiao-Yu Chen Zhi-Chun Gu Hou-Wen Lin A Network Comparison on Safety Profiling of Immune Checkpoint Inhibitors in Advanced Lung Cancer
description	BackgroundImmune checkpoint inhibitors (ICIs) have become one of the standard treatment options for advanced lung cancer. However, adverse events (AEs), particularly immune–related AEs (irAEs), caused by these drugs have aroused public attention. The current network meta-analysis (NMA) aimed to compare the risk of AEs across different ICI–based regimens in patients with advanced lung cancer.MethodsWe systematically searched the PubMed, EMBASE, and Cochrane Library databases (from inception to 19 April 2021) for relevant randomized controlled trials (RCTs) that compared two or more treatments, with at least one ICI administered to patients with advanced lung cancer. The primary outcomes were treatment–related AEs and irAEs, including grade 1–5 and grade 3–5. The secondary outcomes were grade 1–5 and grade 3–5 irAEs in specific organs. Both pairwise and network meta-analyses were conducted for chemotherapy, ICI monotherapy, ICI monotherapy + chemotherapy, dual ICIs therapy, and dual ICIs + chemotherapy for all safety outcomes. Node–splitting analyses were performed to test inconsistencies in network. Sensitivity analyses were adopted by restricting phase III RCTs and studies that enrolled patients with non–small cell lung cancer.ResultsOverall, 38 RCTs involving 22,178 patients with advanced lung cancer were enrolled. Both pooled incidence and NMA indicated that treatments containing chemotherapy increased the risk of treatment–related AEs when compared with ICI-based regimens without chemotherapy. As for grade 1–5 irAEs, dual ICIs + chemotherapy was associated with the highest risk of irAEs (probability in ranking first: 50.5%), followed by dual-ICI therapy (probability in ranking second: 47.2%), ICI monotherapy (probability in ranking third: 80.0%), ICI monotherapy + chemotherapy (probability in ranking fourth: 98.0%), and finally chemotherapy (probability in ranking fifth: 100.0%). In grade 3–5 irAEs, subtle differences were observed; when ranked from least safe to safest, the trend was dual ICIs therapy (60.4%), dual ICIs + chemotherapy (42.5%), ICI monotherapy (76.3%), ICI monotherapy + chemotherapy (95.0%), and chemotherapy (100.0%). Furthermore, detailed comparisons between ICI–based options provided irAE profiles based on specific organ/system and severity.ConclusionsIn consideration of overall immune–related safety profiles, ICI monotherapy + chemotherapy might be a better choice among ICI–based treatments for advanced lung cancer. The safety profiles of ICI–based treatments are various by specific irAEs and their severity.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42021268650
format	article
author	Yi-Dan Yan Jiu-Jie Cui Jie Fu Ying-Jie Su Xiao-Yu Chen Zhi-Chun Gu Hou-Wen Lin
author_facet	Yi-Dan Yan Jiu-Jie Cui Jie Fu Ying-Jie Su Xiao-Yu Chen Zhi-Chun Gu Hou-Wen Lin
author_sort	Yi-Dan Yan
title	A Network Comparison on Safety Profiling of Immune Checkpoint Inhibitors in Advanced Lung Cancer
title_short	A Network Comparison on Safety Profiling of Immune Checkpoint Inhibitors in Advanced Lung Cancer
title_full	A Network Comparison on Safety Profiling of Immune Checkpoint Inhibitors in Advanced Lung Cancer
title_fullStr	A Network Comparison on Safety Profiling of Immune Checkpoint Inhibitors in Advanced Lung Cancer
title_full_unstemmed	A Network Comparison on Safety Profiling of Immune Checkpoint Inhibitors in Advanced Lung Cancer
title_sort	network comparison on safety profiling of immune checkpoint inhibitors in advanced lung cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/9b59e787eb32462b809902f07e7fe08a
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A Network Comparison on Safety Profiling of Immune Checkpoint Inhibitors in Advanced Lung Cancer

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