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.