# Comparative efficacy of combination regimens based on interventional therapy and immune checkpoint inhibitors (ICIs) in patients with intermediate- and advanced-stage hepatocellular carcinoma: a systematic review, meta-analysis, and network meta-analysis

## TL;DR

This study compares different treatment combinations for advanced liver cancer, finding that some regimens offer better survival and response rates.

## Contribution

The study provides a comprehensive network meta-analysis comparing the efficacy and safety of various interventional therapy and ICI combinations in HCC.

## Key findings

- TACE-TKI-Tisle and TACE-TKI-Camrelizumab showed significantly longer progression-free survival compared to other regimens.
- TACE-TKI-Toripalimab demonstrated notable overall survival benefits over other ICI combinations.
- TACE-TKI-Tisle provided a balanced combination of efficacy and safety in treating hepatocellular carcinoma.

## Abstract

Combining interventional therapy with immune checkpoint inhibitors (ICIs) has shown potential benefits in hepatocellular carcinoma (HCC). However, comprehensive evidence on its efficacy and safety remains limited.

A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was conducted to identify eligible studies for single-arm and Bayesian network meta-analyses (NMA). Progression-free survival (PFS) was the primary endpoint, while overall survival (OS), objective response rate (ORR), and grade ≥ 3 adverse events (AEs) were secondary outcomes (PROSPERO: CRD42024619661).

This study included 45 studies (n = 4,738), evaluating 14 distinct regimens. In single-arm analysis, transcatheter arterial chemoembolization (TACE) plus tyrosine-kinase inhibitor (TKI) plus tislelizumab [TACE-TKI-Tisle] yielded a pooled median PFS of 11.7 months (95% confidence interval [CI] 8.02–15.37), an ORR of 72% (95% CI 63–80%), and a grade ≥ 3 AE rate of 24% (95% CI 15–34%). NMA showed that TACE-TKI-Tisle and TACE-TKI-Camrelizumab (Camre) achieved significantly longer PFS than TACE-TKI or TACE alone. TACE-TKI-Toripalimab (Tori) showed OS benefits over TACE-TKI-Camre (HR = 0.43; 95% CI 0.20–0.95) and TACE-TKI-Pembrolizumab (Pembro) (HR = 0.32; 95% CI 0.13–0.81). Cumulative ranking via surface under the cumulative ranking curve (SUCRA) indicated that TACE-TKI-ICI achieved the highest efficacy ranking. TACE-TKI-Tisle and TACE-TKI-Tori ranked highest for PFS/ORR, with TACE-TKI-Tori ranking first for OS (SUCRA = 0.981). While TACE-TKI-ICI combinations were generally associated with more grade ≥ 3 AEs, TACE-TKI-Tisle ranked intermediately for safety (SUCRA = 0.426).

TACE-TKI-ICI combinations show promising efficacy in HCC. TACE-TKI-Tisle offers balanced efficacy and safety, while TACE-TKI-Tori provides notable OS benefits, warranting further validation in prospective studies.

The online version contains supplementary material available at 10.1007/s00262-025-04251-5.