Transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) is the mainstay treatment for unresectable hepatocellular carcinoma (uHCC). However, studies investigating different combinations of agents have shown inconsistent results. Here, we used network meta-analysis (NMA) to compare different agents across 41 studies (36 cohort studies and five RCTs) in 11,540 patients. Multiple RCTs and cohort studies were searched to evaluate TACE combined with different TKIs. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and tumor response. NMA used a random-effects consistency model to pool evidence from direct and indirect comparisons. Hazard ratio (HR) and relative risks (RR) with 95% confidence intervals (CI) were analyzed. Further, heterogeneity and publication bias analyses were performed and agents were ranked. TACE plus lenvatinib provided the maximal OS (Rank probability: 0.7559), PFS (Rank probability: 0.8595), CR (Rank probability: 0.4179), and DCR (Rank probability: 0.3857). TACE plus anlotinib demonstrated the highest PR (p = 0.62649) and ORR (p = 0.51158). SD was more often associated with TACE plus sorafenib (Rank probability: 0.601685). TACE plus lenvatinib provides optimal treatment for uHCC based on the highest ranking of OS, PFS, and DCR rates. However, given the lack of statistically significant OS benefit, shared decision making should include other TKIs as acceptable alternatives.
Keywords: hepatocellular carcinoma; network meta-analysis; transarterial chemoembolization; tyrosine kinase inhibitors.