Cancer Immunology, Immunotherapy · Published 2025-12-19 · Journal article · DOI 10.1007/s00262-025-04255-1 · PMID: 41417116 · PMC · Cited by 2 (Crossref)
Zhenzhen Zhang, Meixia Wang, Guobin Chen, Yanfang Wu, Xiaochun Chen, Xinkun Guo, Boheng Zhang
Abstract Background Hepatic arterial infusion chemotherapy (HAIC) provides sustained high intrahepatic drug exposure with limited systemic toxicity, potentially enhancing antigen release and immune sensitization. This study compared the efficacy and safety of HAIC combined with lenvatinib and PD-1/PD-L1 inhibitors versus systemic chemotherapy-based triple therapy in advanced unresectable intrahepatic cholangiocarcinoma (iCCA). Methods A retrospective analysis of 67 patients with unresectable iCCA treated with HAIC-based triple therapy (n = 32) or systemic triple therapy (n = 35) was conducted. Clinical efficacy, survival, prognostic factors and safety profiles were evaluated. Baseline imbalances were adjusted using inverse probability of treatment weighting (IPTW). Kaplan–Meier and Cox regression analyses before and after IPTW assessed treatment effects on overall survival (OS) and progression-free survival (PFS). Results HAIC-based triple therapy achieved superior tumor control versus systemic therapy, with higher objective response rate (59.4 vs. 20.0%; P < 0.001), disease control rate (90.6 vs. 68.6%; P < 0.001), and tumor shrinkage (+ 6.5 vs. − 1.0 mm; P = 0.002). Local (93.8 vs. 66.7%; P = 0.006) and distant (90.3 vs. 72.7%; P = 0.071) control rates favored HAIC-based triple therapy. After IPTW adjustment, Kaplan–Meier survival analysis showed that HAIC-based triple therapy significantly improved both OS (24.1 vs. 15.5 months; P = 0.010) and PFS (P = 0.020) compared to systemic therapy. In the IPTW-adjusted multivariate Cox regression analysis, HAIC-based triple therapy was associated with a markedly reduced risk of OS (HR [95% CI]: 0.221[0.070–0.693]) and PFS (HR[95% CI]: 0.129[0.028–0.592]). Toxicities were manageable, and immune-related adverse events correlated with reduced progression. Conclusion HAIC-based triple therapy provided superior tumor control, prolonged survival, and preserved hepatic function with acceptable safety in unresectable iCCA.
Abstract from DOAJ. Public domain (CC0 1.0).
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Zhang, Z., Wang, M., Chen, G., et al. (2025). Efficacy and safety of hepatic arterial infusion chemotherapy plus lenvatinib and PD-1/PD-L1 inhibitors versus systemic chemotherapy plus lenvatinib and PD-1/PD-L1 inhibitors in advanced unresectable cholangiocarcinoma: a retrospective cohort study. Cancer Immunology, Immunotherapy. https://doi.org/10.1007/s00262-025-04255-1