{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:41:07Z","timestamp":1790444467735,"version":"4.1.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100008678","name":"Universit\u00e4t Leipzig","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008678","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Biliary tract cancers (BTCs) are a heterogeneous group of malignant cancers with an overall poor prognosis. For more than a decade, the standard palliative first-line therapy was cytotoxic chemotherapy with gemcitabine\/cisplatin. The results of the TOPAZ-1 and KEYNOTE-966 trials have now introduced immune checkpoint inhibitors (ICIs) into first-line therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Between July 2022 and March 2024, we retrospectively analyzed patients with advanced BTC who were treated with gemcitabine\/cisplatin and durvalumab (GCD) at collaborating German university hospitals, tertiary hospitals, and outpatient oncology practices.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 90 patients were enrolled. The median overall survival (mOS) was 16 months, and the median progression-free survival (mPFS) was 5 months. The overall response rate (ORR) was 11.1%, and the disease control rate (DCR) was 41.1%. A perihilar primary tumor was significantly associated with better mPFS, while age group between 70 and 75 years and performance status of ECOG 2 at treatment initiation were significantly associated with poorer mOS. Adverse events (AEs) occurred in a total of 64% of patients. The most common grade 1 and grade 2 AEs included anemia (23%), thrombocytopenia (16%), neutropenia (10%), nausea (14%), and fatigue (16%). Grade 3 and grade 4 AEs included anemia (10%), thrombocytopenia (5%), and neutropenia (11%). Only one case of immune-mediated hypothyroidism (imAE) was documented.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our real-world data support previously reported findings and further validate ICI based therapy as the standard of care for patients with advanced BTCs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00432-025-06239-1","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T11:35:15Z","timestamp":1750246515000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Treatment with gemcitabine\/cisplatin and durvalumab for advanced biliary tract cancer \u2013 real-world data from a multicenter German patient population"],"prefix":"10.1007","volume":"151","author":[{"given":"Florian","family":"Gerhardt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marino","family":"Venerito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Chater","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Mohr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Egerer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo","family":"Lindig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Schindler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Ebel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janett","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maik","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Gehring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"van B\u00f6mmel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"6239_CR1","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.jhep.2023.03.010","volume":"79","author":"D Alvaro","year":"2023","unstructured":"Alvaro D, Gores GJ, Walicki J et al (2023) EASL-ILCA clinical practice guidelines on the management of intrahepatic cholangiocarcinoma. J Hepatol 79:181\u2013208. https:\/\/doi.org\/10.1016\/j.jhep.2023.03.010","journal-title":"J Hepatol"},{"key":"6239_CR2","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/s41575-020-0310-z","volume":"17","author":"JM Banales","year":"2020","unstructured":"Banales JM, Marin JJG, Lamarca A et al (2020) Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol 17:557\u2013588. https:\/\/doi.org\/10.1038\/s41575-020-0310-z","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"6239_CR3","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.jhep.2019.03.013","volume":"71","author":"P Bertuccio","year":"2019","unstructured":"Bertuccio P, Malvezzi M, Carioli G et al (2019) Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma. J Hepatol 71:104\u2013114. https:\/\/doi.org\/10.1016\/j.jhep.2019.03.013","journal-title":"J Hepatol"},{"key":"6239_CR4","doi-asserted-by":"publisher","first-page":"5384","DOI":"10.1158\/1078-0432.CCR-14-1298","volume":"20","author":"AR De Biasi","year":"2014","unstructured":"De Biasi AR, Villena-Vargas J, Adusumilli PS (2014) Cisplatin-induced antitumor immunomodulation: A review of preclinical and clinical evidence. Clin Cancer Res 20:5384\u20135391. https:\/\/doi.org\/10.1158\/1078-0432.CCR-14-1298","journal-title":"Clin Cancer Res"},{"key":"6239_CR5","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.jhep.2022.09.004","volume":"78","author":"JJ Harding","year":"2023","unstructured":"Harding JJ, Khalil DN, Fabris L, Abou-Alfa GK (2023) Rational development of combination therapies for biliary tract cancers. J Hepatol 78:217\u2013228. https:\/\/doi.org\/10.1016\/j.jhep.2022.09.004","journal-title":"J Hepatol"},{"key":"6239_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/cancers15153993","volume":"15","author":"E Kawamura","year":"2023","unstructured":"Kawamura E, Matsubara T, Kawada N (2023) New era of Immune-Based therapy in intrahepatic cholangiocarcinoma. Cancers (Basel) 15:1\u201317. https:\/\/doi.org\/10.3390\/cancers15153993","journal-title":"Cancers (Basel)"},{"key":"6239_CR7","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1016\/S0140-6736(23)00727-4","volume":"401","author":"RK Kelley","year":"2023","unstructured":"Kelley RK, Ueno M, Yoo C et al (2023) Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 401:1853\u20131865. https:\/\/doi.org\/10.1016\/S0140-6736(23)00727-4","journal-title":"Lancet"},{"key":"6239_CR8","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1016\/j.jhep.2022.11.030","volume":"78","author":"G Kendre","year":"2023","unstructured":"Kendre G, Murugesan K, Brummer T et al (2023) Charting co-mutation patterns associated with actionable drivers in intrahepatic cholangiocarcinoma. J Hepatol 78:614\u2013626. https:\/\/doi.org\/10.1016\/j.jhep.2022.11.030","journal-title":"J Hepatol"},{"key":"6239_CR9","unstructured":"Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): S3-Leitlinie Diagnostik und Therapie des Hepatozellul\u00e4ren Karzinoms und bili\u00e4rer Karzinome, Langversion 5.0, 2024, AWMF-Registernummer: 032-053OL"},{"key":"6239_CR10","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.jhep.2019.11.020","volume":"72","author":"V Mazzaferro","year":"2020","unstructured":"Mazzaferro V, Gorgen A, Roayaie S et al (2020) Liver resection and transplantation for intrahepatic cholangiocarcinoma. J Hepatol 72:364\u2013377","journal-title":"J Hepatol"},{"key":"6239_CR11","doi-asserted-by":"publisher","DOI":"10.1002\/ueg2.12656","author":"K Mitzlaff","year":"2024","unstructured":"Mitzlaff K, Kirstein MM, M\u00fcller C et al (2024) Efficacy, safety and differential outcomes of immune-chemotherapy with gemcitabine, cisplatin and durvalumab in patients with biliary tract cancers: A multicenter real world cohort. United Eur Gastroenterol J. https:\/\/doi.org\/10.1002\/ueg2.12656","journal-title":"United Eur Gastroenterol J"},{"key":"6239_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1056\/evidoa2200015","volume":"1","author":"D-Y Oh","year":"2022","unstructured":"Oh D-Y, Ruth He A, Qin S et al (2022) Durvalumab plus gemcitabine and cisplatin in advanced biliary tract Cancer. NEJM Evid 1:1\u201311. https:\/\/doi.org\/10.1056\/evidoa2200015","journal-title":"NEJM Evid"},{"key":"6239_CR12","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1016\/S2468-1253(24)00095-5","volume":"9","author":"D-Y Oh","year":"2024","unstructured":"Oh D-Y, He AR, Bouattour M et al (2024) Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 study. Lancet Gastroenterol Hepatol 9:694\u2013704. https:\/\/doi.org\/10.1016\/S2468-1253(24)00095-5","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"6239_CR14","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1038\/sj.bjc.6605779","volume":"103","author":"T Okusaka","year":"2010","unstructured":"Okusaka T, Nakachi K, Fukutomi A et al (2010) Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: A comparative multicentre study in Japan. Br J Cancer 103:469\u2013474. https:\/\/doi.org\/10.1038\/sj.bjc.6605779","journal-title":"Br J Cancer"},{"key":"6239_CR15","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1007\/s11523-024-01044-1","volume":"19","author":"A Olkus","year":"2024","unstructured":"Olkus A, Tomczak A, Berger AK et al (2024) Durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer: an exploratory analysis of Real-World data. Target Oncol 19:213\u2013221. https:\/\/doi.org\/10.1007\/s11523-024-01044-1","journal-title":"Target Oncol"},{"key":"6239_CR16","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1002\/ijc.33013","volume":"147","author":"SA Piha-Paul","year":"2020","unstructured":"Piha-Paul SA, Oh DY, Ueno M et al (2020) Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: results from the KEYNOTE-158 and KEYNOTE-028 studies. Int J Cancer 147:2190\u20132198. https:\/\/doi.org\/10.1002\/ijc.33013","journal-title":"Int J Cancer"},{"key":"6239_CR17","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1111\/liv.15641","volume":"43","author":"M Rimini","year":"2023","unstructured":"Rimini M, Fornaro L, Lonardi S et al (2023) Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: an early exploratory analysis of real-world data. Liver Int 43:1803\u20131812. https:\/\/doi.org\/10.1111\/liv.15641","journal-title":"Liver Int"},{"key":"6239_CR18","doi-asserted-by":"publisher","first-page":"114199","DOI":"10.1016\/j.ejca.2024.114199","volume":"208","author":"M Rimini","year":"2024","unstructured":"Rimini M, Fornaro L, Rizzato MD et al (2024) Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: A large real-life worldwide population. Eur J Cancer 208:114199. https:\/\/doi.org\/10.1016\/j.ejca.2024.114199","journal-title":"Eur J Cancer"},{"key":"6239_CR19","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.ejca.2021.11.023","volume":"161","author":"H Rumgay","year":"2022","unstructured":"Rumgay H, Ferlay J, de Martel C et al (2022) Global, regional and National burden of primary liver cancer by subtype. Eur J Cancer 161:108\u2013118. https:\/\/doi.org\/10.1016\/j.ejca.2021.11.023","journal-title":"Eur J Cancer"},{"key":"6239_CR20","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1158\/1078-0432.CCR-15-0715","volume":"22","author":"F Sabbatino","year":"2016","unstructured":"Sabbatino F, Villani V, Yearley JH et al (2016) PD-L1 and HLA class i antigen expression and clinical course of the disease in intrahepatic cholangiocarcinoma. Clin Cancer Res 22:470\u2013478. https:\/\/doi.org\/10.1158\/1078-0432.CCR-15-0715","journal-title":"Clin Cancer Res"},{"key":"6239_CR21","doi-asserted-by":"publisher","first-page":"2716","DOI":"10.1200\/JCO.21.02576","volume":"40","author":"AJ Scott","year":"2022","unstructured":"Scott AJ, Sharman R, Shroff RT (2022) Precision medicine in biliary tract Cancer. J Clin Oncol 40:2716\u20132734. https:\/\/doi.org\/10.1200\/JCO.21.02576","journal-title":"J Clin Oncol"},{"key":"6239_CR22","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1056\/NEJMoa0908721","volume":"362","author":"J Valle","year":"2010","unstructured":"Valle J, Wasan H, Palmer DH et al (2010) Cisplatin plus gemcitabine versus gemcitabine for biliary tract Cancer. N Engl J Med 362:1273\u20131281. https:\/\/doi.org\/10.1056\/NEJMoa0908721","journal-title":"N Engl J Med"},{"key":"6239_CR24","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1158\/2159-8290.CD-17-0245","volume":"7","author":"JW Valle","year":"2017","unstructured":"Valle JW, Lamarca A, Goyal L et al (2017) New horizons for precision medicine in biliary tract cancers. Cancer Discov 7:943\u2013962. https:\/\/doi.org\/10.1158\/2159-8290.CD-17-0245","journal-title":"Cancer Discov"},{"key":"6239_CR23","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/S0140-6736(21)00153-7","volume":"397","author":"JW Valle","year":"2021","unstructured":"Valle JW, Kelley RK, Nervi B et al (2021) Biliary tract cancer. Lancet 397:428\u2013444. https:\/\/doi.org\/10.1016\/S0140-6736(21)00153-7","journal-title":"Lancet"},{"key":"6239_CR25","doi-asserted-by":"publisher","first-page":"1690","DOI":"10.1016\/j.jhep.2022.07.022","volume":"77","author":"M Vithayathil","year":"2022","unstructured":"Vithayathil M, Khan SA (2022) Current epidemiology of cholangiocarcinoma in Western countries. J Hepatol 77:1690\u20131698. https:\/\/doi.org\/10.1016\/j.jhep.2022.07.022","journal-title":"J Hepatol"},{"key":"6239_CR26","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.annonc.2022.10.506","volume":"34","author":"A Vogel","year":"2023","unstructured":"Vogel A, Bridgewater J, Edeline J et al (2023) Biliary tract cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up \u2606. Ann Oncol 34:127\u2013140. https:\/\/doi.org\/10.1016\/j.annonc.2022.10.506","journal-title":"Ann Oncol"},{"key":"6239_CR27","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.immuni.2013.06.014","volume":"39","author":"L Zitvogel","year":"2013","unstructured":"Zitvogel L, Galluzzi L, Smyth MJ, Kroemer G (2013) Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. Immunity 39:74\u201388. https:\/\/doi.org\/10.1016\/j.immuni.2013.06.014","journal-title":"Immunity"}],"container-title":["Journal of Cancer Research and Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-025-06239-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00432-025-06239-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-025-06239-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T20:31:17Z","timestamp":1757190677000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00432-025-06239-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,18]]},"references-count":27,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["6239"],"URL":"https:\/\/doi.org\/10.1007\/s00432-025-06239-1","relation":{},"ISSN":["1432-1335"],"issn-type":[{"value":"1432-1335","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,18]]},"assertion":[{"value":"23 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"191"}}