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Hepatic artery infusion chemotherapy combined with lenvatinib and PD‑1 inhibitors in the treatment of intermediate and advanced unresectable hepatocellular carcinoma

  • Authors:
    • Peng Jiang
    • Fengfeng Li
    • Zhenyu Jiang
    • Yiling Sun
    • Fan Yang
    • Lisha Chu
    • Ya Gai
    • Hongjian Wang
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Tengzhou Central People's Hospital Affiliated to Jining Medical College, Tengzhou, Shandong 277500, P.R. China
    Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 437
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    Published online on: July 9, 2025
       https://doi.org/10.3892/ol.2025.15183
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Abstract

Systemic treatment for unresectable advanced hepatocellular carcinoma (HCC) primarily comprises targeted therapy and immunotherapy, which have demonstrated improved therapeutic efficacy compared with chemotherapy. However, the overall efficacy for patients remains below expectations. Hepatic artery infusion chemotherapy (HAIC), a novel approach in the treatment of HCC, involves the direct and continuous administration of chemotherapeutic drugs to liver tumors through catheters. The high concentration of chemotherapeutic drugs not only rapidly reduces tumor burden but also induces immunogenic cell death, promoting the release of tumor‑associated antigens, tumor‑specific antigens and damage‑associated molecular patterns. This markedly enhances the infiltration of dendritic cells and antigen‑specific CD8+ T cells in the tumor microenvironment, thereby enhancing the antitumor effect of programmed cell death protein 1 (PD‑1) inhibitors. Lenvatinib, an anti‑angiogenic agent, not only inhibits neo‑angiogenesis in hepatic tumor tissues but also effectively mitigates VEGF‑mediated immunosuppression. Therefore, the combination of HAIC with lenvatinib and PD‑1 inhibitors exhibits a synergistic effect, overcoming the limitations of individual therapies and maximizing overall antitumor efficacy. The present study demonstrated that this triple therapy enhanced the objective response rate (69.7%; 95% CI, 51.3‑84.4%) and disease control rate (90.9%; 95% CI, 75.7‑98.1%) in patients with unresectable HCC. In terms of survival outcomes, the median progression‑free survival with the triple therapy was 9.7 months (95% CI, 9.3‑11.6), and the median overall survival was 17.4 months (95% CI, 15.4‑24.3). Additionally, the safety profile was favorable, with a low incidence of moderate to severe adverse events, and no treatment‑associated mortalities were reported.
View Figures

Figure 1

Waterfall plot for tumor size changes
of all patients based on the modified Response Evaluation Criteria
in Solid Tumors. PD, progressive disease; PR, partial response.

Figure 2

Kaplan-Meier curve illustrating the
mPFS of all patients who underwent triple therapy vs. dual therapy.
mPFS, median progression-free survival; HR, hazard ratio; CI,
confidence intervals.

Figure 3

Kaplan-Meier curve illustrating the
mOS of all patients who underwent triple therapy vs. dual therapy.
mOS, median overall survival; HR, hazard ratio; CI, confidence
intervals.

Figure 4

Kaplan-Meier curve illustrating the
mPFS of patients with Vp3-4 who underwent triple therapy vs. dual
therapy. mPFS, median progression-free survival.

Figure 5

Kaplan-Meier curve illustrating the
mOS of patients with Vp3-4 who underwent triple therapy vs. dual
therapy. mOS, median overall survival.

Figure 6

Kaplan-Meier curves illustrating the
mPFS of patients with extrahepatic metastasis who underwent triple
therapy vs. dual therapy. mPFS, median progression-free
survival.

Figure 7

Kaplan-Meier curves illustrating the
mOS of patients with extrahepatic metastasis who underwent triple
therapy vs. dual therapy. mOS, median overall survival.
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Copy and paste a formatted citation
Spandidos Publications style
Jiang P, Li F, Jiang Z, Sun Y, Yang F, Chu L, Gai Y and Wang H: Hepatic artery infusion chemotherapy combined with lenvatinib and PD‑1 inhibitors in the treatment of intermediate and advanced unresectable hepatocellular carcinoma. Oncol Lett 30: 437, 2025.
APA
Jiang, P., Li, F., Jiang, Z., Sun, Y., Yang, F., Chu, L. ... Wang, H. (2025). Hepatic artery infusion chemotherapy combined with lenvatinib and PD‑1 inhibitors in the treatment of intermediate and advanced unresectable hepatocellular carcinoma. Oncology Letters, 30, 437. https://doi.org/10.3892/ol.2025.15183
MLA
Jiang, P., Li, F., Jiang, Z., Sun, Y., Yang, F., Chu, L., Gai, Y., Wang, H."Hepatic artery infusion chemotherapy combined with lenvatinib and PD‑1 inhibitors in the treatment of intermediate and advanced unresectable hepatocellular carcinoma". Oncology Letters 30.3 (2025): 437.
Chicago
Jiang, P., Li, F., Jiang, Z., Sun, Y., Yang, F., Chu, L., Gai, Y., Wang, H."Hepatic artery infusion chemotherapy combined with lenvatinib and PD‑1 inhibitors in the treatment of intermediate and advanced unresectable hepatocellular carcinoma". Oncology Letters 30, no. 3 (2025): 437. https://doi.org/10.3892/ol.2025.15183
Copy and paste a formatted citation
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Spandidos Publications style
Jiang P, Li F, Jiang Z, Sun Y, Yang F, Chu L, Gai Y and Wang H: Hepatic artery infusion chemotherapy combined with lenvatinib and PD‑1 inhibitors in the treatment of intermediate and advanced unresectable hepatocellular carcinoma. Oncol Lett 30: 437, 2025.
APA
Jiang, P., Li, F., Jiang, Z., Sun, Y., Yang, F., Chu, L. ... Wang, H. (2025). Hepatic artery infusion chemotherapy combined with lenvatinib and PD‑1 inhibitors in the treatment of intermediate and advanced unresectable hepatocellular carcinoma. Oncology Letters, 30, 437. https://doi.org/10.3892/ol.2025.15183
MLA
Jiang, P., Li, F., Jiang, Z., Sun, Y., Yang, F., Chu, L., Gai, Y., Wang, H."Hepatic artery infusion chemotherapy combined with lenvatinib and PD‑1 inhibitors in the treatment of intermediate and advanced unresectable hepatocellular carcinoma". Oncology Letters 30.3 (2025): 437.
Chicago
Jiang, P., Li, F., Jiang, Z., Sun, Y., Yang, F., Chu, L., Gai, Y., Wang, H."Hepatic artery infusion chemotherapy combined with lenvatinib and PD‑1 inhibitors in the treatment of intermediate and advanced unresectable hepatocellular carcinoma". Oncology Letters 30, no. 3 (2025): 437. https://doi.org/10.3892/ol.2025.15183
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