Systemic therapy plus HAIC versus systemic therapy for hepatocellular carcinoma: a systematic review and meta-analysis.

Background: Hepatic arterial infusion chemotherapy (HAIC) exhibits synergistic anticancer effects with systemic therapy in treating hepatocellular carcinoma (HCC). The approach combining systemic therapy and HAIC is likely to establish a new survival benchmark for advanced HCC. However, related evidence is still lacking.

Method: PubMed, Embase, Cochrane Library, and Web of Science were searched from January 1990 to July 2024. The extracted data were pooled using fixed- or random-effects models and expressed as hazard ratios (HRs) or risk ratios (RRs) with corresponding 95% confidence intervals (CIs). Meta-regression, subgroup analysis, prognostic factor analysis, correlation analysis, as well as trial sequential analysis were further conducted.

Result: Seventeen trials involving 3070 participants were included. Patients receiving HAIC combined systemic therapy displayed superior overall survival (OS) (HR, 0.52; 95% CI, 0.48-0.58), progression-free survival (PFS) (HR, 0.54; 95% CI, 0.46-0.63), objective response rate (ORR) (RR, 2.20; 95% CI, 1.77-2.72) and disease control rate (RR, 1.21; 95% CI, 1.14-1.29) over systemic therapy. Combining HAIC resulted in higher incidences of grade ≥3 manageable adverse events. Subgroup analyses showed that HAIC could bring significant survival improvement for almost all specific populations; however, patients without portal vein tumor thrombosis might not benefit from it (HR, 0.74; 95% CI, 0.53-1.03). Prognostic factor analyses found extra HAIC was a protective factor for both OS (HR, 0.42; 95% CI, 0.34-0.51) and PFS (HR, 0.44; 95% CI, 0.36-0.53). Correlation analyses demonstrated a robust association between ORR and OS when applying systemic therapy with HAIC (P-value = 0.031). In addition, trial sequential analyses visually showed the present data were compelling to draw reliable conclusions.

Conclusion: With manageable toxicity, integrating HAIC with systemic therapy could bring favorable survival benefits for HCC patients. Further evidence is necessary to standardize the integration of HAIC with first-line systemic therapy.