ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1591127
This article is part of the Research TopicIntrahepatic Cholangiocarcinoma: Emerging Insights from Pathobiology to Clinical Translation – Innovative Strategies, Challenges, and OpportunitiesView all articles
Interventional treatment combined with immunotargeted therapy in unresectable combined hepatocellular-cholangiocarcinoma: a real-world retrospective cohort study Running head: Triple therapy for cHCC-CCA
Provisionally accepted
Yan-Song Lin1
Li-Yan Wu1
Lihui Lin2
Xia Yang1Fang-Yi Liu1Yan-Qin Wu2Zhen Ding2Yu-Jing Liang1Jing-Ping Yun1*- 1Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, Guangdong Province, China
- 2The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Background: Evidence-based treatment for unresectable combined hepatocellular-cholangiocarcinoma (cHCC-CCA) has not been established. This study aimed to assess the effectiveness and safety of interventional treatment combined with immunotargeted therapy (IIT) in unresectable cHCC-CCA patients.Methods: Patients with a histological diagnosis of unresectable cHCC-CCA who received IIT therapy from January 2019 to March 2024 were retrospectively enrolled. The study evaluated overall survival (OS), progression-free survival (PFS), tumor responses and safety.Results: A total of 242 cHCC-CCA patients were screened and 51 patients were enrolled for analysis. The median follow-up duration was 15.8 months (95% CI: 12.0-19.7 months). The median OS was 17.8 months (95% CI: 12.4-23.2 months) and the median PFS was 8.9 months (95% CI: 5.8-12.0 months). For overall response, the objective response rate was 41.2% and 58.8% based on RECIST 1.1 and mRECIST, respectively. Patients with primary cHCC-CCA showed significantly prolonged OS (median OS: 21.4 months vs. 11.4 months, p = 0.011) and PFS (median PFS: 9.5 months vs. 4.1 months, p = 0.036) compared to those with recurrent cHCC-CCA. Patients with dominant HCC did not show significant differences for OS (p = 0.835) and PFS (p = 0.553) compared to those with dominant iCCA. Six patients (11.8%) experienced grade ≥3 adverse events, including leukopenia (n=1, 2.0%), neutropenia (n=1, 2.0%), thrombocytopenia (n=2, 3.9%), elevated alanine transaminase (ALT) (n=2, 3.9%), elevated aspartate aminotransferase (AST) (n=2, 3.9%), hypoalbuminemia (n=2, 3.9%), and hyperbilirubinemia (n=1, 2.0%). Immunotherapy was discontinued for 2 patients due to grade ≥3 elevations in ALT and AST.Conclusion: The triple combination of interventional treatment, PD-(L)1 inhibitor, and targeted therapy is an effective and safe approach for unresectable cHCC-CCA patients.
Keywords: Interventional treatment, PD-(L)1 inhibitor, targeted therapy, unresectable combined hepatocellular-cholangiocarcinoma, Outcome
Received: 10 Mar 2025; Accepted: 12 Jun 2025.
Copyright: © 2025 Lin, Wu, Lin, Yang, Liu, Wu, Ding, Liang and Yun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jing-Ping Yun, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, 510060, Guangdong Province, China
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