Treatment-Related Adverse Events with PD-1 or PD-L1 Inhibitors: A Systematic Review and Meta-Analysis

Objective: to evaluate the risk of treatment-related adverse events of different severity and different system with PD-1 or PD-L1 inhibitors. Methods: randomized controlled trials (RCTs) that using PD-1/PD-L1 for cancer treatment were searched in the PubMed, Embase, Cochrane Library, and Web of Scie...

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Autores principales: Yixi Zhang, Bin La, Baosheng Liang, Yangchun Gu
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:75e77664fdfc436687e8ab97cc54265e2021-11-25T18:11:47ZTreatment-Related Adverse Events with PD-1 or PD-L1 Inhibitors: A Systematic Review and Meta-Analysis10.3390/life111112772075-1729https://doaj.org/article/75e77664fdfc436687e8ab97cc54265e2021-11-01T00:00:00Zhttps://www.mdpi.com/2075-1729/11/11/1277https://doaj.org/toc/2075-1729Objective: to evaluate the risk of treatment-related adverse events of different severity and different system with PD-1 or PD-L1 inhibitors. Methods: randomized controlled trials (RCTs) that using PD-1/PD-L1 for cancer treatment were searched in the PubMed, Embase, Cochrane Library, and Web of Science from 1 January 2019 to 31 May 2021. Adverse events data were extracted from clinical trials website or original article by two authors separately. Meta-analysis was used to determine risk ratio (RR) and 95% confidence interval (95% CI) of adverse events in PD-1/PD-L1 inhibitors groups compared to that of control groups. Subgroup analyses were also performed. Results: a total of 5,807 studies were initially identified and after exclusion, 41 studies were included in meta-analysis. All the trials were international multicenter, randomized, phase II/III clinical trials, with the median follow-up of 27.5 months on average. Analysis of all grade adverse events showed that PD-1/PD-L1 inhibitors treatment significantly increased the risk of immune-related adverse events, including pruritus (RR: 2.34, 95% CI: 1.85–2.96), rash (RR: 1.53, 95% CI: 1.25–1.87), ALT elevation (RR 1.54, 95% CI 1.23–1.92), AST elevation (AST: RR 1.49, 95% CI 1.20–1.85), hepatitis (RR: 3.54, 95% CI: 1.96–6.38) and hypothyroid (RR: 5.29, 95% CI: 4.00–6.99) compared with that of control group. Besides that, PD-1/PD-L1 inhibitors were associated with higher risk of adverse events related to respiratory system including cough (RR: 1.33, 95% CI: 1.21–1.48), dyspnea (RR:1.23, 95% CI: 1.12–1.35) and chest pain (RR: 1.26, 95% CI: 1.07–1.47) compared with that of control groups in our meta-analysis and the dyspnea was taken high risk both in all grade and grade 3 or higher (RR: 1.55, 95% CI: 1.13–2.12). The risk of arthralgia was increased with PD-1/PD-L1 inhibitors (RR: 1.27, 95% CI: 1.10–1.47). Although the risk of myalgia was similar with PD-1/PD-L1 inhibitors and control groups, under subgroup analysis, PD-1/PD-L1 inhibitors decreased the risk of myalgia (RR: 0.56, 95% CI: 0.45–0.70) compared with that of chemotherapy. Conclusions: our results provide clear evidence that the risk of treatment-related adverse events in PD-1 or PD-L1 varies widely in different system. In particular, when using PD-1/PD-L1 inhibitors for oncology treatment, besides the common immune-related adverse events like pruritus, rash, hepatitis, and hypothyroid, the respiratory disorders and musculoskeletal disorders, such as cough, dyspnea, arthralgia, and myalgia, should also be taken into consideration.Yixi ZhangBin LaBaosheng LiangYangchun GuMDPI AGarticlecancer treatmentPD-1/PD-L1 inhibitorsadverse eventsmeta-analysisScienceQENLife, Vol 11, Iss 1277, p 1277 (2021)
institution DOAJ
collection DOAJ
language EN
topic cancer treatment
PD-1/PD-L1 inhibitors
adverse events
meta-analysis
Science
Q
spellingShingle cancer treatment
PD-1/PD-L1 inhibitors
adverse events
meta-analysis
Science
Q
Yixi Zhang
Bin La
Baosheng Liang
Yangchun Gu
Treatment-Related Adverse Events with PD-1 or PD-L1 Inhibitors: A Systematic Review and Meta-Analysis
description Objective: to evaluate the risk of treatment-related adverse events of different severity and different system with PD-1 or PD-L1 inhibitors. Methods: randomized controlled trials (RCTs) that using PD-1/PD-L1 for cancer treatment were searched in the PubMed, Embase, Cochrane Library, and Web of Science from 1 January 2019 to 31 May 2021. Adverse events data were extracted from clinical trials website or original article by two authors separately. Meta-analysis was used to determine risk ratio (RR) and 95% confidence interval (95% CI) of adverse events in PD-1/PD-L1 inhibitors groups compared to that of control groups. Subgroup analyses were also performed. Results: a total of 5,807 studies were initially identified and after exclusion, 41 studies were included in meta-analysis. All the trials were international multicenter, randomized, phase II/III clinical trials, with the median follow-up of 27.5 months on average. Analysis of all grade adverse events showed that PD-1/PD-L1 inhibitors treatment significantly increased the risk of immune-related adverse events, including pruritus (RR: 2.34, 95% CI: 1.85–2.96), rash (RR: 1.53, 95% CI: 1.25–1.87), ALT elevation (RR 1.54, 95% CI 1.23–1.92), AST elevation (AST: RR 1.49, 95% CI 1.20–1.85), hepatitis (RR: 3.54, 95% CI: 1.96–6.38) and hypothyroid (RR: 5.29, 95% CI: 4.00–6.99) compared with that of control group. Besides that, PD-1/PD-L1 inhibitors were associated with higher risk of adverse events related to respiratory system including cough (RR: 1.33, 95% CI: 1.21–1.48), dyspnea (RR:1.23, 95% CI: 1.12–1.35) and chest pain (RR: 1.26, 95% CI: 1.07–1.47) compared with that of control groups in our meta-analysis and the dyspnea was taken high risk both in all grade and grade 3 or higher (RR: 1.55, 95% CI: 1.13–2.12). The risk of arthralgia was increased with PD-1/PD-L1 inhibitors (RR: 1.27, 95% CI: 1.10–1.47). Although the risk of myalgia was similar with PD-1/PD-L1 inhibitors and control groups, under subgroup analysis, PD-1/PD-L1 inhibitors decreased the risk of myalgia (RR: 0.56, 95% CI: 0.45–0.70) compared with that of chemotherapy. Conclusions: our results provide clear evidence that the risk of treatment-related adverse events in PD-1 or PD-L1 varies widely in different system. In particular, when using PD-1/PD-L1 inhibitors for oncology treatment, besides the common immune-related adverse events like pruritus, rash, hepatitis, and hypothyroid, the respiratory disorders and musculoskeletal disorders, such as cough, dyspnea, arthralgia, and myalgia, should also be taken into consideration.
format article
author Yixi Zhang
Bin La
Baosheng Liang
Yangchun Gu
author_facet Yixi Zhang
Bin La
Baosheng Liang
Yangchun Gu
author_sort Yixi Zhang
title Treatment-Related Adverse Events with PD-1 or PD-L1 Inhibitors: A Systematic Review and Meta-Analysis
title_short Treatment-Related Adverse Events with PD-1 or PD-L1 Inhibitors: A Systematic Review and Meta-Analysis
title_full Treatment-Related Adverse Events with PD-1 or PD-L1 Inhibitors: A Systematic Review and Meta-Analysis
title_fullStr Treatment-Related Adverse Events with PD-1 or PD-L1 Inhibitors: A Systematic Review and Meta-Analysis
title_full_unstemmed Treatment-Related Adverse Events with PD-1 or PD-L1 Inhibitors: A Systematic Review and Meta-Analysis
title_sort treatment-related adverse events with pd-1 or pd-l1 inhibitors: a systematic review and meta-analysis
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/75e77664fdfc436687e8ab97cc54265e
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AT baoshengliang treatmentrelatedadverseeventswithpd1orpdl1inhibitorsasystematicreviewandmetaanalysis
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