Transarterial chemoembolization combined with immunotherapy-based treatments versus TACE alone in unresectable hepatocellular carcinoma: a systematic review and network meta-analysis

Background The combination of transarterial chemoembolization (TACE) with immune checkpoint inhibitors (ICIs) has emerged as a promising strategy for patients with unresectable hepatocellular carcinoma (uHCC). However, the comparative efficacy and safety of these regimens remain uncertain. We carried out a systematic review and network meta-analysis (NMA) of phase III trials evaluating TACE combined with immunotherapy-based treatments. Materials and methods PubMed/MEDLINE, Scopus, the Cochrane Library, and major oncology congresses were systematically searched for phase III trials comparing TACE alone with TACE plus ICI-based regimens. The primary endpoint was progression-free survival (PFS). Results Five phase III randomly assigned trials involving 2414 patients were included. Compared with TACE alone, TACE plus ICI-based strategies significantly improved PFS [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.63-0.77; fixed-effect model] and objective response rate [risk ratio (RR) 1.41, 95% CI 1.34-1.49]. Pooled overall survival estimate favored combination therapy but did not reach statistical significance (HR 0.88, 95% CI 0.78-1.00). Combination therapy increased grade 3-4 treatment-related adverse events (RR 2.49), serious adverse events (RR 3.10), and treatment-emergent adverse events leading to death (RR 1.73). Subgroup analyses seemed to suggest that patients with albumin-bilirubin (ALBI) score 1 could derive greater PFS benefit than those with an ALBI score of 2 or higher (interaction P = 0.0003). In the NMA, all regimens improved PFS versus TACE, and the P -score ranking for PFS identified atezolizumab plus bevacizumab plus TACE as the highest-ranked regimen ( P -score 0.744). Conclusions Immunotherapy-based treatments combined with TACE consistently improved disease control in uHCC, although the survival benefit appeared more modest. Additional follow-up and head-to-head randomly assigned trials are needed to define the optimal systemic partner for TACE.