Organ‐Specific Responses to Nivolumab Plus Ipilimumab in Advanced Hepatocellular Carcinoma: A Multicenter, Retrospective Study

ABSTRACT Background Immune checkpoint inhibitor (ICI) monotherapy elicits limited intrahepatic responses in patients with advanced hepatocellular carcinoma (HCC). Here, we investigate the organ‐specific objective response rate (OSORR) of nivolumab plus ipilimumab (Nivo/Ipi) combination treatment, co...

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Main Authors: Jung Sun Kim, Youngun Kim, Beodeul Kang, Ilhwan Kim, Hyeyeong Kim, Won Suk Lee, Jung Yong Hong, Ho Yeong Lim, Han Sang Kim, Chang Gon Kim, Sanghoon Jung, Chansik An, Chan Kim, Hong Jae Chon
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.70997
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author Jung Sun Kim
Youngun Kim
Beodeul Kang
Ilhwan Kim
Hyeyeong Kim
Won Suk Lee
Jung Yong Hong
Ho Yeong Lim
Han Sang Kim
Chang Gon Kim
Sanghoon Jung
Chansik An
Chan Kim
Hong Jae Chon
author_facet Jung Sun Kim
Youngun Kim
Beodeul Kang
Ilhwan Kim
Hyeyeong Kim
Won Suk Lee
Jung Yong Hong
Ho Yeong Lim
Han Sang Kim
Chang Gon Kim
Sanghoon Jung
Chansik An
Chan Kim
Hong Jae Chon
author_sort Jung Sun Kim
collection DOAJ
description ABSTRACT Background Immune checkpoint inhibitor (ICI) monotherapy elicits limited intrahepatic responses in patients with advanced hepatocellular carcinoma (HCC). Here, we investigate the organ‐specific objective response rate (OSORR) of nivolumab plus ipilimumab (Nivo/Ipi) combination treatment, considering prior ICI exposure, compared with nivolumab (Nivo) monotherapy. Methods We analyzed 204 lesions from Nivo/Ipi‐treated and 305 lesions from Nivo‐treated patients with advanced HCC at five referral cancer centers in Korea. Organ‐specific response criteria were adopted from Response Evaluation Criteria in Solid Tumors 1.1, according to the indicated sites: the liver, lung, lymph nodes (LNs), and other metastatic sites. Results Nivo/Ipi combination therapy showed OSORRs of 18.1% in the liver, 17.7% in the lungs, 30.0% in LNs, and 12.5% in other metastatic sites. Patients without prior ICI exposure had OSORRs of 29.0% in the liver, 31.3% in the lungs, 33.3% in LNs, and 23.1% in other metastatic sites (72 individual lesions). Conversely, patients with prior ICI exposure had OSORRs of 11.5% in the liver, 11.4% in the lung, 27.8% in LNs, and 7.4% in other metastatic sites (132 individual lesions). Furthermore, patients who achieved a response in the liver or the lung had longer progression‐free and overall survival, compared with those without responses. Nivo monotherapy yielded OSORRs of 13.5%, 25.3%, 39.3%, and 18.4% in the liver, lungs, LNs, and other metastatic sites, respectively. Conclusion Nivo/Ipi combination therapy induced superior intrahepatic responses compared to Nivo monotherapy in patients with advanced HCC without prior ICI exposure, highlighting its potential to overcome liver‐specific immune tolerance.
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spelling doaj-art-85cdc599a9c346f29e27d4ab12a409c42025-08-20T03:46:58ZengWileyCancer Medicine2045-76342025-06-011411n/an/a10.1002/cam4.70997Organ‐Specific Responses to Nivolumab Plus Ipilimumab in Advanced Hepatocellular Carcinoma: A Multicenter, Retrospective StudyJung Sun Kim0Youngun Kim1Beodeul Kang2Ilhwan Kim3Hyeyeong Kim4Won Suk Lee5Jung Yong Hong6Ho Yeong Lim7Han Sang Kim8Chang Gon Kim9Sanghoon Jung10Chansik An11Chan Kim12Hong Jae Chon13Medical Oncology, Department of Internal Medicine CHA Bundang Medical Center, CHA University School of Medicine Seongnam KoreaCHA University School of Medicine Seongnam KoreaMedical Oncology, Department of Internal Medicine CHA Bundang Medical Center, CHA University School of Medicine Seongnam KoreaDivision of Oncology, Department of Internal Medicine Haeundae Paik Hospital, Inje University College of Medicine Busan KoreaDepartment of Internal Medicine Ulsan University Hospital, University of Ulsan College of Medicine Ulsan KoreaMedical Oncology, Department of Internal Medicine CHA Bundang Medical Center, CHA University School of Medicine Seongnam KoreaDivision of Hematology‐Oncology, Department of Medicine Samsung Medical Center, Sungkyunkwan University School of Medicine Seoul KoreaDivision of Hematology‐Oncology, Department of Medicine Samsung Medical Center, Sungkyunkwan University School of Medicine Seoul KoreaYonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine Yonsei University College of Medicine Seoul KoreaYonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine Yonsei University College of Medicine Seoul KoreaDepartment of Radiology CHA Bundang Medical Center, CHA University School of Medicine Seongnam KoreaDepartment of Radiology CHA Bundang Medical Center, CHA University School of Medicine Seongnam KoreaMedical Oncology, Department of Internal Medicine CHA Bundang Medical Center, CHA University School of Medicine Seongnam KoreaMedical Oncology, Department of Internal Medicine CHA Bundang Medical Center, CHA University School of Medicine Seongnam KoreaABSTRACT Background Immune checkpoint inhibitor (ICI) monotherapy elicits limited intrahepatic responses in patients with advanced hepatocellular carcinoma (HCC). Here, we investigate the organ‐specific objective response rate (OSORR) of nivolumab plus ipilimumab (Nivo/Ipi) combination treatment, considering prior ICI exposure, compared with nivolumab (Nivo) monotherapy. Methods We analyzed 204 lesions from Nivo/Ipi‐treated and 305 lesions from Nivo‐treated patients with advanced HCC at five referral cancer centers in Korea. Organ‐specific response criteria were adopted from Response Evaluation Criteria in Solid Tumors 1.1, according to the indicated sites: the liver, lung, lymph nodes (LNs), and other metastatic sites. Results Nivo/Ipi combination therapy showed OSORRs of 18.1% in the liver, 17.7% in the lungs, 30.0% in LNs, and 12.5% in other metastatic sites. Patients without prior ICI exposure had OSORRs of 29.0% in the liver, 31.3% in the lungs, 33.3% in LNs, and 23.1% in other metastatic sites (72 individual lesions). Conversely, patients with prior ICI exposure had OSORRs of 11.5% in the liver, 11.4% in the lung, 27.8% in LNs, and 7.4% in other metastatic sites (132 individual lesions). Furthermore, patients who achieved a response in the liver or the lung had longer progression‐free and overall survival, compared with those without responses. Nivo monotherapy yielded OSORRs of 13.5%, 25.3%, 39.3%, and 18.4% in the liver, lungs, LNs, and other metastatic sites, respectively. Conclusion Nivo/Ipi combination therapy induced superior intrahepatic responses compared to Nivo monotherapy in patients with advanced HCC without prior ICI exposure, highlighting its potential to overcome liver‐specific immune tolerance.https://doi.org/10.1002/cam4.70997advanced HCCimmune checkpoint inhibitorNivolumab monotherapyNivolumab plus ipilimumaborgan‐specific objective response rateprior ICI treatment
spellingShingle Jung Sun Kim
Youngun Kim
Beodeul Kang
Ilhwan Kim
Hyeyeong Kim
Won Suk Lee
Jung Yong Hong
Ho Yeong Lim
Han Sang Kim
Chang Gon Kim
Sanghoon Jung
Chansik An
Chan Kim
Hong Jae Chon
Organ‐Specific Responses to Nivolumab Plus Ipilimumab in Advanced Hepatocellular Carcinoma: A Multicenter, Retrospective Study
Cancer Medicine
advanced HCC
immune checkpoint inhibitor
Nivolumab monotherapy
Nivolumab plus ipilimumab
organ‐specific objective response rate
prior ICI treatment
title Organ‐Specific Responses to Nivolumab Plus Ipilimumab in Advanced Hepatocellular Carcinoma: A Multicenter, Retrospective Study
title_full Organ‐Specific Responses to Nivolumab Plus Ipilimumab in Advanced Hepatocellular Carcinoma: A Multicenter, Retrospective Study
title_fullStr Organ‐Specific Responses to Nivolumab Plus Ipilimumab in Advanced Hepatocellular Carcinoma: A Multicenter, Retrospective Study
title_full_unstemmed Organ‐Specific Responses to Nivolumab Plus Ipilimumab in Advanced Hepatocellular Carcinoma: A Multicenter, Retrospective Study
title_short Organ‐Specific Responses to Nivolumab Plus Ipilimumab in Advanced Hepatocellular Carcinoma: A Multicenter, Retrospective Study
title_sort organ specific responses to nivolumab plus ipilimumab in advanced hepatocellular carcinoma a multicenter retrospective study
topic advanced HCC
immune checkpoint inhibitor
Nivolumab monotherapy
Nivolumab plus ipilimumab
organ‐specific objective response rate
prior ICI treatment
url https://doi.org/10.1002/cam4.70997
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