Transarterial chemoembolization combined with molecular targeted agents plus immune checkpoint inhibitors for unresectable hepatocellular carcinoma beyond the up-to-seven criteria: a propensity score-matching analysis

Ann Med. 2024 Dec;56(1):2419993. doi: 10.1080/07853890.2024.2419993. Epub 2024 Nov 1.

Abstract

Purpose: Not all patients benefit from transarterial chemoembolization (TACE) due to the heterogeneity of the tumour burden in intermediate-stage hepatocellular carcinoma (HCC). To compare the outcomes of transarterial chemoembolization (TACE) combined with molecular-targeted agents plus immune checkpoint inhibitors (TACE-MTAs-ICIs) with those of TACE for patients with unresectable hepatocellular carcinoma (uHCC) that were beyond the up-to-seven criteria.

Patients and methods: Between January 2019 and July 2022, 130 patients diagnosed with uHCC beyond the up-to-seven criteria were retrospectively identified, including 47 patients who received TACE-MTAs-ICIs and 83 patients who received TACE alone. The primary endpoints were overall survival (OS) and progression-free survival (PFS); the secondary endpoints included tumour response and adverse events (AEs).

Results: There were 43 matched patients. The median OS and PFS times in the TACE-MTAs-ICIs group were significantly longer than those in the TACE group (OS: 27.2 vs. 15.9 months, p = 0.007; PFS: 15.4 months vs. 4.8 months, p < 0.001). The objective response rate (ORR) in the TACE-MTAs-ICIs group was higher than that in the TACE group (65.1% vs. 37.2%, p = 0.010). Reversible AEs (grade 3 or 4) occurred differently in TACE-MTAs-ICIs and TACE groups (83.7% vs. 51.2%, p = 0.001). Univariate and multivariate analyses revealed that TACE-MTAs-ICIs treatment was an independent favourable prognostic factor for both PFS and OS (p < 0.001).

Conclusion: For uHCC patients beyond the up-to-seven criteria, TACE-MTAs-ICIs provided superior ORR and OS. Early combined TACE and systemic treatment should shift for patients who are beyond these criteria.

Keywords: Carcinoma; chemoembolization; hepatocellular; immune checkpoint inhibitors; molecular-targeted therapy; therapeutic.

Plain language summary

The ORR and median OS reached 65.1% and 27.2 months, respectively, in the treatment model of TACE-MTAs-ICIs for patients with unresectable HCC that were beyond the up-to-seven criteria.TACE-TKI-ICI yielded a synergistic effect on these patients and was an independent favourable prognostic factor for PFS and OS.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / immunology
  • Carcinoma, Hepatocellular* / mortality
  • Carcinoma, Hepatocellular* / therapy
  • Chemoembolization, Therapeutic* / methods
  • Combined Modality Therapy
  • Female
  • Humans
  • Immune Checkpoint Inhibitors* / administration & dosage
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / immunology
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / pathology
  • Liver Neoplasms* / therapy
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / methods
  • Progression-Free Survival
  • Propensity Score*
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Immune Checkpoint Inhibitors