Organ-Specific Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitor Monotherapy Versus Combination Therapy in Cancer: A Meta-Analysis of Randomized Controlled Trials
BackgroundAlthough combination therapy with immune checkpoint inhibitors (ICIs) provides a promising efficacy in multiple cancers, their use is facing challenges for a high incidence of adverse effects. This meta-analysis was conducted to compare the risks of organ-specific immune-related adverse ev...
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doaj-0be249ff955f40528d14f39659c13f552020-11-25T00:44:43ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-01-011010.3389/fphar.2019.01671494256Organ-Specific Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitor Monotherapy Versus Combination Therapy in Cancer: A Meta-Analysis of Randomized Controlled TrialsLijun Da0Yuanjun Teng1Na Wang2Karen Zaguirre3Yating Liu4Yali Qi5Feixue Song6Department of Oncology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou City, ChinaDepartment of Orthopaedics, Lanzhou University Second Hospital, Lanzhou University, Lanzhou City, ChinaDepartment of Oncology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou City, ChinaDeparment of Surgery, St. Luke’s Medical Center, Quezon City, PhilippinesDepartment of Oncology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou City, ChinaDepartment of Oncology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou City, ChinaDepartment of Oncology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou City, ChinaBackgroundAlthough combination therapy with immune checkpoint inhibitors (ICIs) provides a promising efficacy in multiple cancers, their use is facing challenges for a high incidence of adverse effects. This meta-analysis was conducted to compare the risks of organ-specific immune-related adverse events (IRAEs) associated with ICI monotherapy versus combination therapy among cancer patients.MethodsElectronic databases were systematically searched to include eligible randomized controlled trials (RCTs). Any-grade and 3-5 grade IRAEs (colitis, pneumonitis, hepatitis, hypothyroidism, hyperthyroidism, and hypophysitis) were extracted for meta-analysis. Two reviewers independently assessed the methodological quality. The RevMan 5.3.5 software was used for meta-analysis.ResultsA total of 10 studies involving 8 RCTs with 2716 patients were included in this study. The most common any-grade adverse event was colitis (14.5%), followed by hypothyroidism (13.8%), hepatitis (10.4%), hypophysitis (10.0%), hyperthyroidism (9.3%), and pneumonitis (4.6%). Meta-analysis showed that ICI combination therapy significantly increased the risks of any-grade IRAEs in colitis [relative risk (RR), 3.56; 95% confidence interval (CI), 1.56–8.12; p < 0.05], pneumonitis (RR, 2.31; 95% CI, 1.54–3.45; p < 0.05), hepatitis (RR, 2.54; 95% CI, 1.65–3.91; p < 0.05), hypothyroidism (RR, 2.17; 95% CI, 1.71–2.76; p < 0.05), hyperthyroidism (RR, 3.13; 95% CI, 2.08–4.70; p < 0.05), and hypophysitis (RR, 3.54; 95% CI, 2.07–6.07; p < 0.05) compared with ICI monotherapy, as well as 3-5 grade IRAEs in colitis (RR, 2.50; 95% CI, 1.62–3.86; p < 0.05), pneumonitis (RR, 1.99; 95% CI, 1.00–3.93; p = 0.05), and hepatitis (RR, 2.70; 95% CI, 1.29–5.63; p < 0.05).ConclusionsThis meta-analysis demonstrated that, compared with ICI monotherapy, patients receiving ICI combination therapy significantly increased organ-specific IRAEs in colitis, hypothyroidism, hepatitis, hypophysitis, hyperthyroidism, and pneumonitis. The incidence and severity of organ-specific IRAEs were drug and dose independent.https://www.frontiersin.org/article/10.3389/fphar.2019.01671/fullimmune checkpoint inhibitorcombination immunotherapyorgan specificadverse eventsmeta-analysis |
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language |
English |
format |
Article |
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DOAJ |
author |
Lijun Da Yuanjun Teng Na Wang Karen Zaguirre Yating Liu Yali Qi Feixue Song |
spellingShingle |
Lijun Da Yuanjun Teng Na Wang Karen Zaguirre Yating Liu Yali Qi Feixue Song Organ-Specific Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitor Monotherapy Versus Combination Therapy in Cancer: A Meta-Analysis of Randomized Controlled Trials Frontiers in Pharmacology immune checkpoint inhibitor combination immunotherapy organ specific adverse events meta-analysis |
author_facet |
Lijun Da Yuanjun Teng Na Wang Karen Zaguirre Yating Liu Yali Qi Feixue Song |
author_sort |
Lijun Da |
title |
Organ-Specific Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitor Monotherapy Versus Combination Therapy in Cancer: A Meta-Analysis of Randomized Controlled Trials |
title_short |
Organ-Specific Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitor Monotherapy Versus Combination Therapy in Cancer: A Meta-Analysis of Randomized Controlled Trials |
title_full |
Organ-Specific Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitor Monotherapy Versus Combination Therapy in Cancer: A Meta-Analysis of Randomized Controlled Trials |
title_fullStr |
Organ-Specific Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitor Monotherapy Versus Combination Therapy in Cancer: A Meta-Analysis of Randomized Controlled Trials |
title_full_unstemmed |
Organ-Specific Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitor Monotherapy Versus Combination Therapy in Cancer: A Meta-Analysis of Randomized Controlled Trials |
title_sort |
organ-specific immune-related adverse events associated with immune checkpoint inhibitor monotherapy versus combination therapy in cancer: a meta-analysis of randomized controlled trials |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2020-01-01 |
description |
BackgroundAlthough combination therapy with immune checkpoint inhibitors (ICIs) provides a promising efficacy in multiple cancers, their use is facing challenges for a high incidence of adverse effects. This meta-analysis was conducted to compare the risks of organ-specific immune-related adverse events (IRAEs) associated with ICI monotherapy versus combination therapy among cancer patients.MethodsElectronic databases were systematically searched to include eligible randomized controlled trials (RCTs). Any-grade and 3-5 grade IRAEs (colitis, pneumonitis, hepatitis, hypothyroidism, hyperthyroidism, and hypophysitis) were extracted for meta-analysis. Two reviewers independently assessed the methodological quality. The RevMan 5.3.5 software was used for meta-analysis.ResultsA total of 10 studies involving 8 RCTs with 2716 patients were included in this study. The most common any-grade adverse event was colitis (14.5%), followed by hypothyroidism (13.8%), hepatitis (10.4%), hypophysitis (10.0%), hyperthyroidism (9.3%), and pneumonitis (4.6%). Meta-analysis showed that ICI combination therapy significantly increased the risks of any-grade IRAEs in colitis [relative risk (RR), 3.56; 95% confidence interval (CI), 1.56–8.12; p < 0.05], pneumonitis (RR, 2.31; 95% CI, 1.54–3.45; p < 0.05), hepatitis (RR, 2.54; 95% CI, 1.65–3.91; p < 0.05), hypothyroidism (RR, 2.17; 95% CI, 1.71–2.76; p < 0.05), hyperthyroidism (RR, 3.13; 95% CI, 2.08–4.70; p < 0.05), and hypophysitis (RR, 3.54; 95% CI, 2.07–6.07; p < 0.05) compared with ICI monotherapy, as well as 3-5 grade IRAEs in colitis (RR, 2.50; 95% CI, 1.62–3.86; p < 0.05), pneumonitis (RR, 1.99; 95% CI, 1.00–3.93; p = 0.05), and hepatitis (RR, 2.70; 95% CI, 1.29–5.63; p < 0.05).ConclusionsThis meta-analysis demonstrated that, compared with ICI monotherapy, patients receiving ICI combination therapy significantly increased organ-specific IRAEs in colitis, hypothyroidism, hepatitis, hypophysitis, hyperthyroidism, and pneumonitis. The incidence and severity of organ-specific IRAEs were drug and dose independent. |
topic |
immune checkpoint inhibitor combination immunotherapy organ specific adverse events meta-analysis |
url |
https://www.frontiersin.org/article/10.3389/fphar.2019.01671/full |
work_keys_str_mv |
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