Local–regional therapy combined with immune checkpoint inhibitors and lenvatinib versus immune checkpoint inhibitors plus chemotherapy in advanced intrahepatic cholangiocarcinoma: a multicenter cohort study

Abstract Background Chemotherapy combined with immune checkpoint inhibitors (ICIs) remains the first-line treatment for advanced intrahepatic cholangiocarcinoma (ICC) but is limited by suboptimal efficacy. While local–regional therapy plus ICIs and lenvatinib (triple therapy) has demonstrated antitu...

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Main Authors: Shuofeng Li, Guanhua Yu, Mingming Wang, Shi Feng, An Zhang, Yu Wu, Zixiang Zhou, Shanshan Wang, Yihong Zhang, Mingjian Piao, Chengjie Li, Ziyu Xun, Boyu Sun, Jiongyuan Li, Nan Zhang, Hu Li, Yongliang Sun, Wen Zhang, Zhenyu Zhu, Haitao Zhao
Format: Article
Language:English
Published: Springer 2025-07-01
Series:Cancer Immunology, Immunotherapy
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Online Access:https://doi.org/10.1007/s00262-025-04129-6
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author Shuofeng Li
Guanhua Yu
Mingming Wang
Shi Feng
An Zhang
Yu Wu
Zixiang Zhou
Shanshan Wang
Yihong Zhang
Mingjian Piao
Chengjie Li
Ziyu Xun
Boyu Sun
Jiongyuan Li
Nan Zhang
Hu Li
Yongliang Sun
Wen Zhang
Zhenyu Zhu
Haitao Zhao
author_facet Shuofeng Li
Guanhua Yu
Mingming Wang
Shi Feng
An Zhang
Yu Wu
Zixiang Zhou
Shanshan Wang
Yihong Zhang
Mingjian Piao
Chengjie Li
Ziyu Xun
Boyu Sun
Jiongyuan Li
Nan Zhang
Hu Li
Yongliang Sun
Wen Zhang
Zhenyu Zhu
Haitao Zhao
author_sort Shuofeng Li
collection DOAJ
description Abstract Background Chemotherapy combined with immune checkpoint inhibitors (ICIs) remains the first-line treatment for advanced intrahepatic cholangiocarcinoma (ICC) but is limited by suboptimal efficacy. While local–regional therapy plus ICIs and lenvatinib (triple therapy) has demonstrated antitumor activity in biliary tract cancers, its role in ICC remains unclear. This multicenter study compared the effectiveness and tolerability of this triple therapy versus chemotherapy plus ICIs in advanced ICC. Methods Advanced ICC patients receiving first-line local–regional therapy (radiotherapy, hepatic arterial infusion chemotherapy, or transarterial chemoembolization) plus ICIs and lenvatinib or chemotherapy plus ICIs were screened. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), adverse events (AEs). Results A total of 78 patients receiving triple therapy and 70 patients receiving chemotherapy plus ICIs were included. The triple therapy group exhibited significantly prolonged median PFS (10.8 vs. 7.6 months, P = 0.011) and median OS (18.5 vs. 15.0 months, P = 0.040), along with higher ORR (51.3% vs. 27.1%) and DCR (85.9% vs. 81.4%). Grade 3–4 AEs occurred more frequently in the triple therapy group (60.3% vs. 58.6%), this difference lacked statistical significance (P = 0.968). No grade 5 events were reported, and all AEs were manageable. Multivariate analysis identified CEA as an independent prognostic factor for PFS and OS. Conclusion Local–regional therapy plus ICIs and lenvatinib demonstrated superior efficacy and manageable toxicity, establishing it as a viable first-line regimen for advanced ICC.
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spelling doaj-art-9f0b8161e8ab479a9f3eac33ba7d6b4e2025-08-20T03:05:29ZengSpringerCancer Immunology, Immunotherapy1432-08512025-07-0174811310.1007/s00262-025-04129-6Local–regional therapy combined with immune checkpoint inhibitors and lenvatinib versus immune checkpoint inhibitors plus chemotherapy in advanced intrahepatic cholangiocarcinoma: a multicenter cohort studyShuofeng Li0Guanhua Yu1Mingming Wang2Shi Feng3An Zhang4Yu Wu5Zixiang Zhou6Shanshan Wang7Yihong Zhang8Mingjian Piao9Chengjie Li10Ziyu Xun11Boyu Sun12Jiongyuan Li13Nan Zhang14Hu Li15Yongliang Sun16Wen Zhang17Zhenyu Zhu18Haitao Zhao19Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Hepatobiliary Surgery, The Fifth Medical Center of PLA General HospitalDepartment of Hepatobiliary and Pancreatic Surgery, China–Japan Friendship HospitalNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Hepatobiliary Surgery, The Fifth Medical Center of PLA General HospitalDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeAbstract Background Chemotherapy combined with immune checkpoint inhibitors (ICIs) remains the first-line treatment for advanced intrahepatic cholangiocarcinoma (ICC) but is limited by suboptimal efficacy. While local–regional therapy plus ICIs and lenvatinib (triple therapy) has demonstrated antitumor activity in biliary tract cancers, its role in ICC remains unclear. This multicenter study compared the effectiveness and tolerability of this triple therapy versus chemotherapy plus ICIs in advanced ICC. Methods Advanced ICC patients receiving first-line local–regional therapy (radiotherapy, hepatic arterial infusion chemotherapy, or transarterial chemoembolization) plus ICIs and lenvatinib or chemotherapy plus ICIs were screened. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), adverse events (AEs). Results A total of 78 patients receiving triple therapy and 70 patients receiving chemotherapy plus ICIs were included. The triple therapy group exhibited significantly prolonged median PFS (10.8 vs. 7.6 months, P = 0.011) and median OS (18.5 vs. 15.0 months, P = 0.040), along with higher ORR (51.3% vs. 27.1%) and DCR (85.9% vs. 81.4%). Grade 3–4 AEs occurred more frequently in the triple therapy group (60.3% vs. 58.6%), this difference lacked statistical significance (P = 0.968). No grade 5 events were reported, and all AEs were manageable. Multivariate analysis identified CEA as an independent prognostic factor for PFS and OS. Conclusion Local–regional therapy plus ICIs and lenvatinib demonstrated superior efficacy and manageable toxicity, establishing it as a viable first-line regimen for advanced ICC.https://doi.org/10.1007/s00262-025-04129-6Biliary tract cancerIntrahepatic cholangiocarcinomaLocal–regional therapyChemotherapyImmunotherapyTargeted therapy
spellingShingle Shuofeng Li
Guanhua Yu
Mingming Wang
Shi Feng
An Zhang
Yu Wu
Zixiang Zhou
Shanshan Wang
Yihong Zhang
Mingjian Piao
Chengjie Li
Ziyu Xun
Boyu Sun
Jiongyuan Li
Nan Zhang
Hu Li
Yongliang Sun
Wen Zhang
Zhenyu Zhu
Haitao Zhao
Local–regional therapy combined with immune checkpoint inhibitors and lenvatinib versus immune checkpoint inhibitors plus chemotherapy in advanced intrahepatic cholangiocarcinoma: a multicenter cohort study
Cancer Immunology, Immunotherapy
Biliary tract cancer
Intrahepatic cholangiocarcinoma
Local–regional therapy
Chemotherapy
Immunotherapy
Targeted therapy
title Local–regional therapy combined with immune checkpoint inhibitors and lenvatinib versus immune checkpoint inhibitors plus chemotherapy in advanced intrahepatic cholangiocarcinoma: a multicenter cohort study
title_full Local–regional therapy combined with immune checkpoint inhibitors and lenvatinib versus immune checkpoint inhibitors plus chemotherapy in advanced intrahepatic cholangiocarcinoma: a multicenter cohort study
title_fullStr Local–regional therapy combined with immune checkpoint inhibitors and lenvatinib versus immune checkpoint inhibitors plus chemotherapy in advanced intrahepatic cholangiocarcinoma: a multicenter cohort study
title_full_unstemmed Local–regional therapy combined with immune checkpoint inhibitors and lenvatinib versus immune checkpoint inhibitors plus chemotherapy in advanced intrahepatic cholangiocarcinoma: a multicenter cohort study
title_short Local–regional therapy combined with immune checkpoint inhibitors and lenvatinib versus immune checkpoint inhibitors plus chemotherapy in advanced intrahepatic cholangiocarcinoma: a multicenter cohort study
title_sort local regional therapy combined with immune checkpoint inhibitors and lenvatinib versus immune checkpoint inhibitors plus chemotherapy in advanced intrahepatic cholangiocarcinoma a multicenter cohort study
topic Biliary tract cancer
Intrahepatic cholangiocarcinoma
Local–regional therapy
Chemotherapy
Immunotherapy
Targeted therapy
url https://doi.org/10.1007/s00262-025-04129-6
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