Neoadjuvant Immune Checkpoint Inhibitors in hepatocellular carcinoma: a meta-analysis and systematic review

Front Immunol. 2024 Feb 19:15:1352873. doi: 10.3389/fimmu.2024.1352873. eCollection 2024.

Abstract

Background: Neoadjuvant immunotherapy has demonstrated beneficial outcomes in various cancer types; however, standardized protocols for neoadjuvant immunotherapy in hepatocellular carcinoma (HCC) are currently lacking. This systematic review and meta-analysis aims to investigate the reliability of neoadjuvant immunotherapy's efficacy and safety in the context of HCC.

Methods: A systematic search was conducted across PubMed (MEDLINE), EMBASE, the Web of Science, the Cochrane Library, and conference proceedings to identify clinical trials involving resectable HCC and neoadjuvant immunotherapy. Single-arm meta-analyses were employed to compute odds ratios and 95% confidence intervals (CIs). Heterogeneity analysis, data quality assessment, and subgroup analyses based on the type of immunotherapy drugs and combination therapies were performed. This meta-analysis is registered in PROSPERO (identifier CRD42023474276).

Results: This meta-analysis included 255 patients from 11 studies. Among resectable HCC patients, neoadjuvant immunotherapy exhibited an overall major pathological response (MPR) rate of 0.47 (95% CI 0.31-0.70) and a pathological complete response (pCR) rate of 0.22 (95% CI 0.14-0.36). The overall objective response rate (ORR) was 0.37 (95% CI 0.20-0.69), with a grade 3-4 treatment-related adverse event (TRAE) incidence rate of 0.35 (95% CI 0.24-0.51). Furthermore, the combined surgical resection rate was 3.08 (95% CI 1.66-5.72). Subgroup analysis shows no significant differences in the efficacy and safety of different single-agent immunotherapies; the efficacy of dual ICIs (Immune Checkpoint Inhibitors) combination therapy is superior to targeted combined immunotherapy and monotherapy, while the reverse is observed in terms of safety.

Discussion: Neoadjuvant immunotherapy presents beneficial outcomes in the treatment of resectable HCC. However, large-scale, high-quality experiments are warranted in the future to provide robust data support.

Keywords: hepatocellular carcinoma (HCC); immunotherapy; meta-analysis; neoadjuvant; resectable; systematic review.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular* / drug therapy
  • Humans
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Liver Neoplasms* / drug therapy
  • Neoadjuvant Therapy
  • Reproducibility of Results

Substances

  • Immune Checkpoint Inhibitors

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Guangdong Provincial Key Area Research and Development Program Project (Grant No. 2020B1111100011), National Natural Science Foundation of China (Grant No. 82274605), National Natural Science Foundation of China (Grant No. 82205220), the General Project of Shenzhen Science and Technology Innovation Commission (Grant No. JCYJ20190807101603569), the Project of Shenzhen Longgang District Science and Technology Innovation Bureau (Grant No. LGKCYLWS2022), the Yulong Talent Training Plan Project of Shenzhen Hospital of Beijing University of Traditional Chinese Medicine (Grant No. 2020-BUCMSZYLR05), the Medicine and Health Project of Zhejiang pvovince, China (Grant No.2021KY1174) and the Science and Technology Program of Zhoushan, China (Grant No.2021C31059).