Efficacy and safety of hepatic arterial infusion chemotherapy combined with tyrosine kinase inhibitors and PD-1 inhibitors for unresectable hepatocellular carcinoma: a meta-analysis

Abstract

The triplet combination of hepatic arterial infusion chemotherapy (HAIC), a tyrosine kinase inhibitor (TKI), and a programmed cell death-1 (PD-1) inhibitor has emerged as a highly promising strategy for unresectable hepatocellular carcinoma (uHCC). This study aimed to comprehensively evaluate the efficacy and safety of this triple-therapy compared with the dual-therapy of a TKI plus a PD-1 inhibitor. We systematically searched PubMed, Embase, and the Cochrane Library for randomized controlled trials or comparative cohort studies that assessed HAIC plus a TKI and a PD-1 inhibitor (H-T-P) versus a TKI plus a PD-1 inhibitor (T-P) for uHCC. The primary endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). The secondary endpoint was treatment-related adverse events (AEs). A random-effects model was employed to pool data, calculating hazard ratios (HRs) or relative risks (RRs) with their 95% confidence intervals (CIs). A total of 12 studies involving 2,386 patients with uHCC were included. Compared with T-P dual therapy, the H-T-P triple therapy was associated with significantly improved OS (HR, 0.51; 95%CI, 0.47-0.56; P  < 0.001) and PFS (HR, 0.59; 95%CI, 0.51-0.68; P  < 0.001). Furthermore, the H-T-P group demonstrated a significantly higher ORR (RR, 1.97; 95%CI, 1.73-2.24; P  < 0.001) and DCR (RR, 1.19; 95%CI, 1.11-1.28; P  < 0.001). Regarding safety, while no significant difference was observed in the overall incidence of all-grade AEs ( P  = 0.238), the incidence of grade ≥3 AEs was significantly higher in the triple-therapy arm (RR, 1.29; 95%CI, 1.13-1.48; P  = 0.004), consisting primarily of manageable hepatotoxicity and hematologic toxicities. Our findings indicate that for patients with uHCC, the H-T-P triple-therapy regimen is superior to dual therapy in terms of survival benefits and tumor response. The associated increase in severe toxicity is considered predictable and clinically manageable. https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420251113276.