Efficacy and safety of hepatic arterial infusion chemotherapy combined with tyrosine kinase inhibitors and PD-1 inhibitors for unresectable hepatocellular carcinoma: a meta-analysis
8 affiliations
- 1Department of Hepatobiliary Surgery, Loudi Central Hospital
- 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hunan University of Medicine
- 3Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University
- 4Department of General Surgery, The People’s Hospital of Liangping District
- 5Department of Gynecologic Oncology, Chongqing University Cancer Hospital
- 6Department of General Surgery, University-Town Hospital of Chongqing Medical University
- 7Department of Gastroenterology and Hepatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
- 8Department of Hematology and Oncology, The First Affiliated Hospital of Hunan University of Medicine
Abstract
Background: 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.
Methods: 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).
Results: 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.
Conclusion: 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.
Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420251113276.
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BibTeX
@article{ouyang2026efficacy,
title = {{Efficacy and safety of hepatic arterial infusion chemotherapy combined with tyrosine kinase inhibitors and PD-1 inhibitors for unresectable hepatocellular carcinoma: a meta-analysis}},
author = {Renbin Ouyang and Xiaocheng Li and Kun Huang and Duke Chen and Yaowei Yang and Xinmin Li and Liming Zhu and Chunzhi Liang},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1896692},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1896692/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Efficacy and safety of hepatic arterial infusion chemotherapy combined with tyrosine kinase inhibitors and PD-1 inhibitors for unresectable hepatocellular carcinoma: a meta-analysis
AU - Renbin Ouyang
AU - Xiaocheng Li
AU - Kun Huang
AU - Duke Chen
AU - Yaowei Yang
AU - Xinmin Li
AU - Liming Zhu
AU - Chunzhi Liang
PY - 2026
DA - 2026/10/08
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1896692
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1896692/full
AB - Background: 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. Methods: 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). Results: 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. Conclusion: 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. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420251113276.
SN - 2234-943X
ER -