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Efficacy and safety of immune checkpoint inhibitors in elderly patients with primary liver cancer: a retrospective, multicenter, real-world cohort study

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Abstract

Background

There is still no specific real-world data regarding the clinical activity of immune checkpoint inhibitors in the elderly with liver cancer. Our study aimed to compare the efficacy and safety of immune checkpoint inhibitors between patients aged ≥ 65 years and the younger group, while exploring their differences in genomic background and tumor microenvironment.

Methods

This retrospective study was conducted at two hospitals in China and included 540 patients treated with immune checkpoint inhibitors for primary liver cancer between January 2018 and December 2021. Patients’ medical records were reviewed for clinical and radiological data and oncologic outcomes. The genomic and clinical data of patients with primary liver cancer were extracted and analyzed from TCGA-LIHC, GSE14520, and GSE140901 datasets.

Results

Ninety-two patients were classified as elderly and showed better progression-free survival (P = 0.027) and disease control rate (P = 0.014). No difference was observed in overall survival (P = 0.69) or objective response rate (P = 0.423) between the two age groups. No significant difference was reported concerning the number (P = 0.824) and severity (P = 0.421) of adverse events. The enrichment analyses indicated that the elderly group was linked to lower expression of oncogenic pathways, such as PI3K-Akt, Wnt, and IL-17. The elderly had a higher tumor mutation burden than younger patients.

Conclusions

Our results indicated that immune checkpoint inhibitors might exhibit better efficacy in the elderly with primary liver cancer, with no increased adverse events. Differences in genomic characteristics and tumor mutation burden may partially explain these results.

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Data availability

Due to the privacy of patients, the data related to patients cannot be available for public access but can be obtained from the corresponding author on reasonable request approved by the institutional review board of all enrolled centers.

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Acknowledgements

We thank all the participants in our study.

Funding

This work was supported by the National Nature Science Foundation of China (No. 81972897, 82172751), China Postdoctoral Science Foundation (No. 2021M701629), Guangzhou Science and Technology Project (No. 202201011183), and Guangdong Natural Science Foundation (No. 2022A1515110656).

Author information

Author notes

  1. Lushan Xiao, Yanxia Liao, Jiaren Wang, Qimei Li, and Hongbo Zhu have been contributed equally to this work.

Authors and Affiliations

  1. Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China

    Lushan Xiao, Yanxia Liao, Jiaren Wang, Qimei Li, Hao Cui, Lin Zeng & Li Liu

  2. Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China

    Lushan Xiao, Yanxia Liao, Jiaren Wang, Qimei Li, Chang Hong, Ruining Li, Jingzhe He, Hao Cui, Lin Zeng & Li Liu

  3. Department of Medical Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan Province, China

    Hongbo Zhu

  4. Department of Medical Oncology, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Clinical Research Center for Cancer, Nanchang, 330029, China

    Hanzhi Dong

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  1. Lushan Xiao
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Contributions

Conceptualisation: LX and LZ; Resources: HD, LX and LL; Investigation and methodology: HC; Data curation: LZ, HZ, JW, QL, and CH; Formal analysis and visualisation: LZ; Validation: RL, and JH; Writing-original draft: LZ, and HZ; Writing-review and editing: LX and YL; Funding acquisition: LL; Supervision: HZ and LL. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Hao Cui, Hanzhi Dong, Lin Zeng or Li Liu.

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Conflict of interest

All the authors declare that they have no confict of interest.

Consent to participate

The need for obtaining informed consent was waived owing to the retrospective study design.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The study design was approved by the Medical Ethics Committee of Nanfang Hospital, Southern Medical University (approval number: NFEC-2021-048).

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Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Fig. 1 Volcano plot of DEGs from GSE140901. DEGs, differentially expressed genes (EPS 1936 KB)

262_2023_3417_MOESM2_ESM.eps

Supplementary Fig. 2 (a-c) GO enrichment analyses of the DEGs identified from TCGA-LIHC (a), GSE14520 (b), and GSE140901 (c). (d) The upregulated and downregulated pathways associated with DEGs of KEGG analysis in GSE140901. GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes (EPS 10317 KB)

Supplementary file3 (DOCX 18 KB)

Supplementary file4 (DOCX 17 KB)

Supplementary file5 (DOCX 18 KB)

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Xiao, L., Liao, Y., Wang, J. et al. Efficacy and safety of immune checkpoint inhibitors in elderly patients with primary liver cancer: a retrospective, multicenter, real-world cohort study. Cancer Immunol Immunother 72, 2299–2308 (2023). https://doi.org/10.1007/s00262-023-03417-3

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