Evaluation of Targeted Agents for Advanced and Unresectable Hepatocellular Carcinoma: A Network Meta-Analysis

Objective: To evaluate different targeted anticancer agents for patients with advanced or unresectable hepatocellular carcinoma (HCC) based on network meta-analysis. Methods: Literature retrieval was conducted in globally recognized databases, namely, MEDLINE, PMC, EMBASE and Cochrane Central to find relevant randomized controlled trials (RCTs). Relative parametric data, including overall survival (OS), progression-free survival (PFS) and adverse event (AE), were quantitatively pooled and estimated based on the Bayesian theorem. The values of the surface under the cumulative ranking (SUCRA) probabilities regarding each parameter were calculated and ranked. Node-splitting analysis was performed to test the inconsistency of the main results, and publication bias was assessed by examining funnel-plot symmetry. Results: After a detailed review, 31 RCTs containing 20 different agents or combinations were finally included for network meta-analysis. For patients without previously systematic treatments, lenvatinib had the best clinical effects on OS (SUCRA, 0.22), and apatinib was superior regarding PFS (SUCRA, 0.41) and AE (SUCRA, 0.15). For patients who received previously targeted agents therapies, regorafenib exhibited the superior clinical effects on OS (SUCRA, 0.42) and PFS (SUCRA, 0.30), while codrituzumab showed the greatest safety benefit on AE (SUCRA, 0.75). Moreover, node-splitting analysis and funnel-plot symmetries illustrated no inconsistency or obvious publication bias in the current study. Conclusions: According to current evidence, lenvatinib and apatinib had superior clinical effects for patients without previously systematic treatments, and regorafenib seemed to be more suitable for patients with previously targeted agent therapies. However, our conclusions still need more statistical validations, and more high-quality trials are expected.