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

BACKGROUND: 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. METHODS: 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). FINDINGS: 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). CONCLUSION: 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.