{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T12:52:09Z","timestamp":1783947129511,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100013058","name":"Jiangsu Provincial Key Research and Development Program","doi-asserted-by":"publisher","award":["BE2019747"],"award-info":[{"award-number":["BE2019747"]}],"id":[{"id":"10.13039\/501100013058","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871988"],"award-info":[{"award-number":["81871988"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82002584"],"award-info":[{"award-number":["82002584"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82103009"],"award-info":[{"award-number":["82103009"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Immune checkpoint inhibitor (ICI) combination therapy offers a new option for treatment of unresectable intrahepatic cholangiocarcinoma (uICC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To compare the effect of different anti\u2010PD\u20101 combination therapies as the first\u2010line treatments for uICC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study included 318 patients who received chemotherapy alone (Chemo), anti\u2010PD\u20101 plus chemotherapy (ICI\u2010chemo), anti\u2010PD\u20101 plus targeted therapy (ICI\u2010target) or anti\u2010PD\u20101 plus targeted therapy and chemotherapy (ICI\u2010target\u2010chemo) as first line for uICC from 22 centres in China. The primary endpoint was progression\u2010free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR) and safety.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with ICI\u2010chemo (median PFS [mPFS], 6.3\u2009months; HR: 0.61, 95% CI: 0.42\u20130.88; <jats:italic>p<\/jats:italic>\u2009=\u20090.008; median OS [mOS], 10.7\u2009months; HR: 0.61, 95% CI: 0.39\u20130.94; <jats:italic>p<\/jats:italic>\u2009=\u20090.026), ICI\u2010target (7.2\u2009months; HR: 0.54, 95% CI: 0.36\u20130.80; <jats:italic>p<\/jats:italic>\u2009=\u20090.002; 15.8\u2009months; HR: 0.54, 95% CI: 0.35\u20130.84; <jats:italic>p<\/jats:italic>\u2009=\u20090.006) or ICI\u2010target\u2010chemo (6.9\u2009months; HR: 0.65, 95% CI: 0.47\u20130.90; <jats:italic>p<\/jats:italic>\u2009=\u20090.009; 14.4\u2009months; HR: 0.47, 95% CI: 0.31\u20130.70; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) achieved better clinical outcomes than those with Chemo (3.8\u2009months; 9.3\u2009months). ICI\u2010target was not inferior to ICI\u2010chemo in survival outcomes (HR for PFS: 0.88, 95% CI: 0.55\u20131.42; <jats:italic>p<\/jats:italic>\u2009=\u20090.614; HR for OS: 0.89, 95% CI: 0.51\u20131.55; <jats:italic>p<\/jats:italic>\u2009=\u20090.680). ICI\u2010target\u2010chemo yielded similar prognoses as ICI\u2010chemo (HR for PFS: 1.07, 95% CI: 0.70\u20131.62; <jats:italic>p<\/jats:italic>\u2009=\u20090.764; HR for OS: 0.77, 95% CI: 0.45\u20131.31; <jats:italic>p<\/jats:italic>\u2009=\u20090.328) and ICI\u2010target (HR for PFS: 1.20, 95% CI: 0.77\u20131.88; <jats:italic>p<\/jats:italic>\u2009=\u20090.413; HR for OS: 0.86, 95% CI: 0.51\u20131.47; <jats:italic>p<\/jats:italic>\u2009=\u20090.583) but resulted in more adverse events (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001; <jats:italic>p<\/jats:italic>\u2009=\u20090.010). Multivariable and propensity score analyses supported these findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Among patients with uICC, ICI\u2010chemo or ICI\u2010target provided more survival benefits than Chemo while achieving comparable prognoses and fewer adverse events than ICI\u2010target\u2010chemo.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.17623","type":"journal-article","created":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T22:54:07Z","timestamp":1687647247000},"page":"611-622","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effect of different <scp>PD<\/scp>\u20101 inhibitor combination therapies for unresectable intrahepatic cholangiocarcinoma"],"prefix":"10.1111","volume":"58","author":[{"given":"Zhengqing","family":"Lei","sequence":"first","affiliation":[{"name":"Hepato\u2010Pancreato\u2010Biliary Center Zhongda Hospital, School of Medicine, Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihu","family":"Ma","sequence":"additional","affiliation":[{"name":"Hepato\u2010Pancreato\u2010Biliary Center Zhongda Hospital, School of Medicine, Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anfeng","family":"Si","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology Qin Huai Medical District of Jinling Hospital, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer, Chinese Academy of Sciences  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Facai","family":"Yang","sequence":"additional","affiliation":[{"name":"Hepato\u2010Pancreato\u2010Biliary Center Zhongda Hospital, School of Medicine, Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiushi","family":"Yu","sequence":"additional","affiliation":[{"name":"Hepato\u2010Pancreato\u2010Biliary Center Zhongda Hospital, School of Medicine, Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haolan","family":"Tang","sequence":"additional","affiliation":[{"name":"Hepato\u2010Pancreato\u2010Biliary Center Zhongda Hospital, School of Medicine, Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianru","family":"Xiao","sequence":"additional","affiliation":[{"name":"Hepato\u2010Pancreato\u2010Biliary Center Zhongda Hospital, School of Medicine, Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahua","family":"Zhou","sequence":"additional","affiliation":[{"name":"Hepato\u2010Pancreato\u2010Biliary Center Zhongda Hospital, School of Medicine, Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hepatic Surgery II The Eastern Hepatobiliary Surgery Hospital, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufu","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery General Hospital of Northern Theater Command  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology the First Hospital of China Medical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowen","family":"Yin","sequence":"additional","affiliation":[{"name":"Interventional Radiology Department Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of General Surgery Huashan Hospital &amp; Cancer Metastasis Institute, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology of PLA Cancer Center Jinling Hospital  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of General Surgery The First Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Decai","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery The Affiliated Drum Tower Hospital, Medical School of Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Luo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tumor Immunopathology, Ministry of Education of China Institute of Pathology and Southwest Hospital, Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery Zibo Central Hospital  Zibo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9852-2661","authenticated-orcid":false,"given":"Maolin","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Pancreatic Surgery Fujian Provincial Hospital  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianhai","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary The Second Affiliated Hospital of Army Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Jiangxi Provincial Clinical Research Center for General Surgery Disease The Second Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingdong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Affiliated Hospital of North Sichuan Medical College  Nanchong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongyi","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Mengchao Hepatobiliary Hospital, Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dequan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology Maanshan People's Hospital  Maanshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingsong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Oncology Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Wu","sequence":"additional","affiliation":[{"name":"Hepatobiliary Center, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxiang","family":"Xia","sequence":"additional","affiliation":[{"name":"Hepatobiliary Center, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hepatic Surgery VI The Eastern Hepatobiliary Surgery Hospital, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixing","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Hepatic Surgery VI The Eastern Hepatobiliary Surgery Hospital, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Center of Interventional Radiology &amp; Vascular Surgery, Department of Radiology Zhongda Hospital, School of Medicine, Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Gao","sequence":"additional","affiliation":[{"name":"Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"H\u00fcser","sequence":"additional","affiliation":[{"name":"Department of Surgery TUM School of Medicine, Klinikum rechts der Isar, Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan Y.","family":"Lau","sequence":"additional","affiliation":[{"name":"Faculty of Medicine The Chinese University of Hong Kong  Hong Kong Special Administrative Region China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianqiang","family":"Song","sequence":"additional","affiliation":[{"name":"Liver Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer Tianjin Medical University Cancer Institute and Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqun","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Hepatic Surgery VI The Eastern Hepatobiliary Surgery Hospital, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Hepatic Surgery IV The Eastern Hepatobiliary Surgery Hospital, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6500-7535","authenticated-orcid":false,"given":"Zhangjun","family":"Cheng","sequence":"additional","affiliation":[{"name":"Hepato\u2010Pancreato\u2010Biliary Center Zhongda Hospital, School of Medicine, Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.10.009"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0908721"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.09.004"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33013"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2020.0930"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1915745"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00252-7"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.00808"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2200015"},{"key":"e_1_2_10_11_1","volume-title":"NCCN Clinical Practice Guidelines in Oncology. Hepatobiliary Cancers (Version 2, 2022)","author":"National Comprehensive Cancer Network (NCCN)"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001240"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2019-000367"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.648068"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2021.11.012"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2020.2814"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00153-7"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3375"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13975"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.6607"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/00273171.2011.568786"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.09.025"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00604-5"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.01307"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-020-0413-z"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-1543"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(23)00727\u20104"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010022\u201000615\u2010z"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.05.009"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31175"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.751391"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01317-7"}],"container-title":["Alimentary Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.17623","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,6]],"date-time":"2024-01-06T04:50:44Z","timestamp":1704516644000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apt.17623"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,22]]},"references-count":31,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["10.1111\/apt.17623"],"URL":"https:\/\/doi.org\/10.1111\/apt.17623","archive":["Portico"],"relation":{},"ISSN":["0269-2813","1365-2036"],"issn-type":[{"value":"0269-2813","type":"print"},{"value":"1365-2036","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,22]]},"assertion":[{"value":"2023-05-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}