{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T16:59:33Z","timestamp":1785517173495,"version":"3.56.0"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Gastroenterol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Durvalumab plus gemcitabine\u2013cisplatin (GCD) has become a standard first-line therapy for advanced biliary tract cancer (BTC) following the TOPAZ-1 trial. However, whether the survival benefit observed in trial-eligible patients can be generalized to broader real-world populations remains uncertain. We evaluated the impact of TOPAZ-1 eligibility on the effectiveness of GCD in routine clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this multicenter retrospective cohort study, 610 patients with unresectable or recurrent BTC treated with first-line GCD (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009268) or gemcitabine\u2013cisplatin (GC) (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009342) at 19 Japanese institutions were analyzed. Patients were classified according to TOPAZ-1 eligibility criteria. Overall survival (OS) was compared between treatment groups in the entire cohort and stratified by eligibility status. Multivariable Cox models were constructed separately for eligible and ineligible patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 610 patients, 324 (53.1%) met TOPAZ-1 eligibility criteria. In the overall cohort, GCD was associated with longer OS than GC (median, 13.7 vs 11.3\u00a0months;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009). Among eligible patients, GCD significantly improved OS compared with GC (18.0 vs 13.1\u00a0months;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004), whereas no significant difference was observed among ineligible patients (10.8 vs 10.0\u00a0months;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.675). However, the interaction between treatment and TOPAZ-1 eligibility was not statistically significant (\n                      <jats:italic>p<\/jats:italic>\n                      for interaction\u2009=\u20090.162).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this real-world cohort, the survival benefit of GCD appeared to be primarily observed in patients meeting TOPAZ-1 eligibility criteria. Trial-based eligibility may influence the magnitude of benefit from immunochemotherapy in advanced BTC, underscoring the importance of patient selection in routine practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00535-026-02412-6","type":"journal-article","created":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T14:33:54Z","timestamp":1776004434000},"page":"1170-1180","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of TOPAZ-1 eligibility on the survival benefit of durvalumab plus gemcitabine\u2013cisplatin in advanced biliary tract cancer: a multicenter real-world study"],"prefix":"10.1007","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2926-9973","authenticated-orcid":false,"given":"Hisashi","family":"Kosaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rie","family":"Sugimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Kinoshita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Kakizaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Sakata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyonori","family":"Yamai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Hatanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshifumi","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Morikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Hanaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruki","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Toyoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Sanuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misaki","family":"Yokoi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Shibata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Fukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhito","family":"Kawata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Amaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Hidaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Naganuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keishi","family":"Sugimachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Kaibori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,12]]},"reference":[{"issue":"6","key":"2412_CR1","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1053\/j.gastro.2013.10.013","volume":"145","author":"SI Ilyas","year":"2013","unstructured":"Ilyas SI, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology. 2013;145(6):1215\u201329. https:\/\/doi.org\/10.1053\/j.gastro.2013.10.013.","journal-title":"Gastroenterology"},{"issue":"6","key":"2412_CR2","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1016\/j.jhep.2014.01.021","volume":"60","author":"J Bridgewater","year":"2014","unstructured":"Bridgewater J, Galle PR, Khan SA, Llovet JM, Park J-W, Patel T, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol. 2014;60(6):1268\u201389. https:\/\/doi.org\/10.1016\/j.jhep.2014.01.021.","journal-title":"J Hepatol"},{"issue":"14","key":"2412_CR3","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, Cunningham D, Anthoney A, Maraveyas A, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273\u201381. https:\/\/doi.org\/10.1056\/NEJMoa0908721.","journal-title":"N Engl J Med"},{"issue":"8","key":"2412_CR4","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2200015","volume":"1","author":"DY Oh","year":"2022","unstructured":"Oh DY, He AR, Qin S, Chen LT, Okusaka T, Vogel A, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. 2022;1(8):EVIDoa2200015. https:\/\/doi.org\/10.1056\/EVIDoa2200015.","journal-title":"NEJM Evid"},{"issue":"12","key":"2412_CR5","doi-asserted-by":"publisher","DOI":"10.1111\/liv.70428","volume":"45","author":"M Rimini","year":"2025","unstructured":"Rimini M, Fornaro L, Ikeda M, Abidoye O, Lucchetti J, Antonuzzo L, et al. Durvalumab in advanced biliary tract cancer: real-world data from a large cohort of patients across multiple international centers. Liver Int. 2025;45(12):e70428. https:\/\/doi.org\/10.1111\/liv.70428.","journal-title":"Liver Int"},{"issue":"12","key":"2412_CR6","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-024-03842-y","volume":"73","author":"P Reimann","year":"2024","unstructured":"Reimann P, Mavroeidi IA, Burghofer J, Taghizadeh H, Webersinke G, Kasper S, et al. Exploring the impact of durvalumab on biliary tract cancer: insights from real-world clinical data. Cancer Immunol Immunother. 2024;73(12):251. https:\/\/doi.org\/10.1007\/s00262-024-03842-y.","journal-title":"Cancer Immunol Immunother"},{"issue":"6","key":"2412_CR7","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-025-06239-1","volume":"151","author":"F Gerhardt","year":"2025","unstructured":"Gerhardt F, M\u00fcller C, Venerito M, Chater J, Mohr R, Egerer M, et al. Treatment with gemcitabine\/cisplatin and durvalumab for advanced biliary tract cancer: real-world data from a multicenter German patient population. J Cancer Res Clin Oncol. 2025;151(6):191. https:\/\/doi.org\/10.1007\/s00432-025-06239-1.","journal-title":"J Cancer Res Clin Oncol"},{"issue":"8","key":"2412_CR8","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyae306","volume":"30","author":"W-K Huang","year":"2025","unstructured":"Huang W-K, Tang Y-J, Wu C-E, Hou M-M, Hsu H-C, Su P-J, et al. Real-world effectiveness and prognostic factors of durvalumab plus chemotherapy in a multicentric cohort with advanced biliary tract cancer. Oncologist. 2025;30(8):oyae306. https:\/\/doi.org\/10.1093\/oncolo\/oyae306.","journal-title":"Oncologist"},{"issue":"3","key":"2412_CR9","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1007\/s11523-024-01060-1","volume":"19","author":"M Rimini","year":"2024","unstructured":"Rimini M, Masi G, Lonardi S, Nichetti F, Pressiani T, Lavacchi D, et al. Durvalumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin in biliary tract cancer: a real-world retrospective, multicenter study. Target Oncol. 2024;19(3):359\u201370. https:\/\/doi.org\/10.1007\/s11523-024-01060-1.","journal-title":"Target Oncol"},{"issue":"8","key":"2412_CR10","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1016\/S2468-1253(24)00095-5","volume":"9","author":"DY Oh","year":"2024","unstructured":"Oh DY, He AR, Bouattour M, Okusaka T, Qin S, Chen LT, et al. 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. 2024;9(8):694\u2013704. https:\/\/doi.org\/10.1016\/S2468-1253(24)00095-5.","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"1","key":"2412_CR11","doi-asserted-by":"publisher","first-page":"149","DOI":"10.2217\/fon.09.136","volume":"6","author":"CSD Roxburgh","year":"2010","unstructured":"Roxburgh CSD, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol. 2010;6(1):149\u201363. https:\/\/doi.org\/10.2217\/fon.09.136.","journal-title":"Future Oncol"},{"issue":"6","key":"2412_CR12","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1200\/JCO.2014.57.9151","volume":"33","author":"PJ Johnson","year":"2015","unstructured":"Johnson PJ, Berhane S, Kagebayashi C, Satomura S, Teng M, Reeves HL, et al. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach\u2014the ALBI grade. J Clin Oncol. 2015;33(6):550\u20138. https:\/\/doi.org\/10.1200\/JCO.2014.57.9151.","journal-title":"J Clin Oncol"},{"issue":"5","key":"2412_CR13","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1159\/000525488","volume":"11","author":"E Gigante","year":"2022","unstructured":"Gigante E, Hobeika C, Le Bail B, Paradis V, Tougeron D, Lequoy M, et al. Systemic treatments with tyrosine kinase inhibitor and platinum-based chemotherapy in patients with unresectable or metastatic hepatocholangiocarcinoma. Liver Cancer. 2022;11(5):460\u201373. https:\/\/doi.org\/10.1159\/000525488.","journal-title":"Liver Cancer"},{"issue":"6","key":"2412_CR14","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1016\/j.xkme.2021.08.008","volume":"3","author":"H Seethapathy","year":"2021","unstructured":"Seethapathy H, Herrmann SM, Sise ME. Immune checkpoint inhibitors and kidney toxicity: advances in diagnosis and management. Kidney Med. 2021;3(6):1074\u201381. https:\/\/doi.org\/10.1016\/j.xkme.2021.08.008.","journal-title":"Kidney Med"},{"issue":"6","key":"2412_CR15","doi-asserted-by":"publisher","first-page":"e379","DOI":"10.1093\/oncolo\/oyad001","volume":"28","author":"BC Tiu","year":"2023","unstructured":"Tiu BC, Strohbehn IA, Zhao S, Ouyang T, Hanna P, Wang Q, et al. Safety of immune checkpoint inhibitors in patients with advanced chronic kidney disease: a retrospective cohort study. Oncologist. 2023;28(6):e379\u201390. https:\/\/doi.org\/10.1093\/oncolo\/oyad001.","journal-title":"Oncologist"},{"issue":"5","key":"2412_CR16","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1016\/j.jhep.2025.05.020","volume":"83","author":"F Castet","year":"2025","unstructured":"Castet F, Fabregat-Franco C, Bridgewater J, Kim JW, Rimini M, La Casta A, et al. Association of candidate surrogate endpoints with overall survival in advanced biliary tract cancer. J Hepatol. 2025;83(5):1102\u201315. https:\/\/doi.org\/10.1016\/j.jhep.2025.05.020.","journal-title":"J Hepatol"},{"issue":"2","key":"2412_CR17","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s11523-023-00953-x","volume":"18","author":"M Rimini","year":"2023","unstructured":"Rimini M, Persano M, Tada T, Suda G, Shimose S, Kudo M, et al. Real-world data for atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma: how does adherence to the IMbrave150 trial inclusion criteria impact prognosis? Target Oncol. 2023;18(2):221\u201333. https:\/\/doi.org\/10.1007\/s11523-023-00953-x.","journal-title":"Target Oncol"}],"container-title":["Journal of Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00535-026-02412-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00535-026-02412-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00535-026-02412-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T16:05:58Z","timestamp":1785513958000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00535-026-02412-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,12]]},"references-count":17,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["2412"],"URL":"https:\/\/doi.org\/10.1007\/s00535-026-02412-6","relation":{},"ISSN":["0944-1174","1435-5922"],"issn-type":[{"value":"0944-1174","type":"print"},{"value":"1435-5922","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,12]]},"assertion":[{"value":"20 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that there is no conflict of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the institutional review board of Kansai Medical University (Approval No. 2023320). It was performed in accordance with the Declaration of Helsinki.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}}]}}