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Severe immune-related adverse events of immune checkpoint inhibitors for advanced non-small cell lung cancer: a network meta-analysis of randomized clinical trials

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Abstract

Objective

A complete toxicity profile, toxicity profile, and safety ranking of immune checkpoint inhibitors (ICIs) for treatment of advanced non-small cell lung cancer (NSCLC) will be provided in this network meta-analysis.

Methods

We searched 14 randomized clinical trials (RCTs) including 9572 NSCLC patients by PubMed, EMBASE, Cochrane, and ClinicalTrials.gov. Randomized pairwise and network meta-analyses were used to compare the incidence of severe immune-related adverse events (irAEs) across different ICIs-based treatments using risk ratios (RRs) and 95% confidence intervals (CI).

Results

For severe dermatologic irAEs, the corresponding ranking of incidences of the nine groups from high to low was: nivolumab + ipilimumab + platinum (79.1%), pembrolizumab (75.2%), nivolumab + ipilimumab (72.9%), camrelizumab + platinum (64.9%), atezolizumab + platinum (47.4%), nivolumab (44.2%), durvalumab (40.5%), pembrolizumab + platinum (15.5%), platinum-based chemotherapy (10.3%). For severe colitis, the corresponding ranking of incidences of the seven groups from high to low was: nivolumab + ipilimumab + platinum (72.4%), nivolumab (63.1%), atezolizumab + platinum (56.9%), durvalumab (56.6%), pembrolizumab (54.9%), pembrolizumab + platinum (38.6%), platinum-based chemotherapy (7.4%). For severe endocrine irAEs, the corresponding ranking of incidences of the nine groups from high to low was: durvalumab (74.3%), atezolizumab + platinum (54.5%), nivolumab + ipilimumab (54.0%), camrelizumab + platinum (51.7%), nivolumab + ipilimumab + platinum (51.6%), pembrolizumab + platinum (49.8%), pembrolizumab (49.2%), nivolumab (46.3%), platinum-based chemotherapy (18.6%). For severe pneumonitis, the corresponding ranking of incidences of the nine groups from high to low was: nivolumab (84.3%), pembrolizumab (84.1%), durvalumab (66.1%), camrelizumab + platinum (61.4%), atezolizumab + platinum (50%), pembrolizumab + platinum (43.4%), platinum-based chemotherapy (16.2%), atezolizumab (6.2%). For severe hepatitis, the corresponding ranking of incidences of the eight groups from high to low was: pembrolizumab (68.8%), nivolumab + ipilimumab + platinum (65%), pembrolizumab + platinum (64.6%), durvalumab (57.9%), nivolumab (47.1%), atezolizumab + platinum (43.4%), camrelizumab + platinum (42%), platinum-based chemotherapy (11.2%).

Conclusions

In addition to platinum-based chemotherapy, pembrolizumab + platinum for severe dermatologic irAEs and colitis, nivolumab for severe endocrine irAEs, atezolizumab for severe pneumonitis, camrelizumab + platinum for severe hepatitis may be associated with lower rates of irAEs than other immune-based regimens.

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Availability of data and material

The data of this paper came from articles of various large RCTs and Clinical Trails.gov. I’m ready to provide the data if needed.

Code availability

Stata13.0, R (version 4.0.1) (CoreTeam 2019, Vienna, Austria) and JAGS (version 4.3.0).

Abbreviations

95% CI:

95% Confidence interval

CTLA4:

Cytotoxic T lymphocyte-associated antigen-4

ICI:

Immune checkpoint inhibitor

ICIs:

Immune checkpoint inhibitors

irAEs:

Immune-related adverse events

MCMC:

Markov chain Monte Carlo

NMA:

Network meta-analysis

NSCLC:

Non-small cell lung cancer

PD-1:

Programmed cell death receptor 1

PD-L1:

Programmed cell death ligand-1

PD-L2:

Programmed cell death ligand-2

PRISMA:

Preferred reporting items for systematic reviews and meta-analysis

RCTs:

Randomized clinical trials

RRs:

Risk ratios

SUCRA:

Surface under the cumulative ranking curve

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Authors and Affiliations

  1. Zhejiang Medical and Health Group Hangzhou Hospital, Hangzhou, Zhejiang, China

    Jingjing Gu, Xiaowen Jiang, Jianhua Wen & Xiaoming Zheng

  2. Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China

    Lei Shi & Hu Cai

  3. Center of General Surgery, The Xixi Hospital of Hangzhou, 2 Hengbu Street, Liuxia Town, Xihu District, Hangzhou, Zhejiang, China

    Weidong Zhang

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  1. Jingjing Gu
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  2. Lei Shi
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  3. Xiaowen Jiang
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  4. Jianhua Wen
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  6. Hu Cai
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Contributions

WZ gave substantial contributions to the conception or the design of the manuscript, JG and LS helped in acquisition, analysis, and interpretation of the data. XJ, JW, XZ, and HC have participated in the data collection of this article. All authors have participated to drafting the manuscript, WZ revised it critically. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Weidong Zhang.

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We declare that we have no financial or personal relationships with other people or organizations that could inappropriately influence our work; there is no professional or other personal interest of any nature or kind in any product, service, or company.

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This network meta-analysis is a data reintegration based on the original data, which does not involve ethics.

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Gu, J., Shi, L., Jiang, X. et al. Severe immune-related adverse events of immune checkpoint inhibitors for advanced non-small cell lung cancer: a network meta-analysis of randomized clinical trials. Cancer Immunol Immunother 71, 2239–2254 (2022). https://doi.org/10.1007/s00262-022-03140-5

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