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02 19, 2024;22 (1): 75.

Comparison of immune checkpoint inhibitors related to pulmonary adverse events: a retrospective analysis of clinical studies and network meta-analysis.

Baohui Hong, Bin Du, Rong Chen, Caiyun Zheng, Ruping Ni, Maobai Liu, Jing Yang
Author Information
  1. Baohui Hong: Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, China.
  2. Bin Du: Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, China.
  3. Rong Chen: Department of Anesthesiology, The Second Hospital of Sanming City, Sanming, China.
  4. Caiyun Zheng: Fuqing City Hospital Affiliated to Fujian Medical University, Fuzhou, China.
  5. Ruping Ni: Department of Pharmacy, The First Hospital of Nanping City, Nanping, China.
  6. Maobai Liu: Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, China. liumb0591@fjmu.edu.cn.
  7. Jing Yang: Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, China. Jiangyang@fjmu.edu.cn.
PMID: 38373990 DOI: 10.1186/s12916-024-03285-3

Abstract

BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed tumor treatment. However, the risk of pulmonary adverse events (PAEs) associated with ICI combination therapy is still unclear. We aimed to provide a PAE overview and risk ordering of ICIs used in tumor treatment.
METHODS: We searched the databases of PubMed, PsycINFO, Embase, Cochrane Library, CINAHL, Web of Science, Scopus, and clinical trial websites during January 2011-April 2023 to identify phase II and III randomized clinical trials (RCTs) and single-arm clinical trials wherein at least one treatment arm received ICIs (e.g., ICI monotherapy, a combination of two ICIs, or ICIs in combination with conventional cancer therapy). We reported the results of PAEs. Additionally, we compared risks of PAEs between different drug classes using a Bayesian network meta-analysis.
RESULTS: Among 143 RCTs and 24 single-arm trials, the incidence of all-grade and grade 3-4 PAEs were highest with programmed death L1 (PD-L1) plus cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and plus chemotherapy and anti-PD1 plus anti-CTLA4, the lowest with targeted therapy drug plus chemotherapy and anti-PD1 plus anti-PDL1. Anti-PD1 plus anti-CTLA4 and plus chemotherapy was the intervention with the highest risk for all-grade and 3-4 grade PAEs, and the intervention with the lowest risk was chemotherapy and anti-PD1 plus anti-PDL1. In terms of all-grade PAEs, chemotherapy was safer than ICI monotherapy. Except for the anti-PD1 plus anti-PDL1 regimen, no significant difference in the risk of grade 3-4 PAEs was detected between dual-ICIs and single-ICIs. Furthermore, the risk of PAEs associated with nivolumab, pembrolizumab, and atezolizumab may be dose dependent.
CONCLUSIONS: In the single-drug regimen, anti-PD1 caused the greatest incidence of PAEs. The risk of PAEs was higher with all single-ICIs than with chemotherapy. However, no significant difference in the risk of PAEs was detected between single-ICIs. In the combined regimen, anti-PD1 plus anti-CTLA4 and plus chemotherapy showed the greatest risk of PAEs, but there were no significant differences in risk between dual-ICIs and single-ICIs.

Keywords

Immune checkpoint inhibitors Pulmonary adverse events Treatment-related adverse events Tumor

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Grants

  1. 2019-ZQN-39/the Key Project for Youth Academic Talents from the Health and Family Planning Commission of Fujian Province
  2. 2023Y4006/University-Industry cooperation project from Fujian Provincial Department of Science and Technology

MeSH Term

Humans
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Incidence
Neoplasms
Network Meta-Analysis
Clinical Trials as Topic

Chemicals

Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Meta-Analysis Journal Article Research Support, Non-U.S. Gov't

Word Cloud

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