{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T17:22:13Z","timestamp":1794244933785,"version":"4.9.0"},"reference-count":11,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>We assessed immune-mediated adverse events (imAEs) in the TOPAZ-1 (NCT03875235) study of durvalumab plus gemcitabine and cisplatin (GemCis) in advanced biliary tract cancer (aBTC).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Participants were randomized 1:1 to durvalumab (1500 mg) or placebo, plus GemCis (gemcitabine [1000 mg\/m2] and cisplatin [25 mg\/m2]) intravenously, followed by durvalumab (1500 mg) or placebo Q4W. We assessed imAE incidence, time to onset (TTO), and association with overall survival (OS).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In durvalumab (n\u2005=\u2005338) versus placebo (n\u2005=\u2005342), imAEs were reported in 13.9% versus 4.7% of participants, with median TTO of 127.0 versus 86.5 days, respectively. OS HR for durvalumab versus placebo in participants with imAEs was 0.59 (95% CI, 0.30-1.23) and was 0.83 (95% CI, 0.70-1.00) in participants without imAEs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Durvalumab demonstrated an OS benefit versus placebo in aBTC, irrespective of imAEs, which were mostly low grade and manageable. The results in these subgroups were consistent with the overall primary analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration<\/jats:title>\n                  <jats:p>ClinicalTrials.gov NCT03875235<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyaf148","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T11:19:43Z","timestamp":1751887183000},"source":"Crossref","is-referenced-by-count":6,"title":["Immune-mediated adverse events in the randomized phase 3 TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3349-5604","authenticated-orcid":false,"given":"Lorenzo","family":"Antonuzzo","sequence":"first","affiliation":[{"name":"Clinical Oncology Unit, Careggi University Hospital, and Department of Experimental and Clinical Medicine, University of Florence , Largo Brambilla 3, 50134, Florence ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Osaka International Cancer Institute , 3-1-69, Otemae, Chuo-Ku, Osaka , 541-8567,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6502-2612","authenticated-orcid":false,"given":"Joon Oh","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine , 81 Irwon-ro, Gangnam-gu, Seoul 06351 ,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aumkhae","family":"Sookprasert","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Department of Medicine, Faculty of Medicine, Khon Kaen University , 123 Mittraparp Road, Muang, Khon Kaen 40002 ,","place":["Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roopinder","family":"Gillmore","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Royal Free Hospital , Pond Street, London, NW3 2QG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5800-1901","authenticated-orcid":false,"given":"Sheng-Shun","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital , 1650 Taiwan Boulevard, Section 4, Taichung, 40705 ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Cundom","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Metab\u00f3licas , Libertad 836, C1012AAR Cdad, Buenos Aires ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mila","family":"Petrova","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, MHAT Nadezhda , Blaga Vest Str, 1330 Sofia ,","place":["Bulgaria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Vaccaro","sequence":"additional","affiliation":[{"name":"Providence Cancer Institute , 4805 Northeast Glisan Street, Portland, OR 97213 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marielle","family":"Holmblad","sequence":"additional","affiliation":[{"name":"Oncology R&D, Late-Stage Development , AstraZeneca, 1 Medimmune Way, Gaithersburg , MD 20878-2204 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"\u017botkiewicz","sequence":"additional","affiliation":[{"name":"Oncology Biometrics, Late Oncology Statistics, AstraZeneca , Post\u0119pu 14, 02-676 Warsaw ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Wang","sequence":"additional","affiliation":[{"name":"Oncology R&D, Late-Stage Development, AstraZeneca , 430 East 29 Street, New York, NY 10016 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"Rokutanda","sequence":"additional","affiliation":[{"name":"Oncology R&D, Late-Stage Development , AstraZeneca, 1 Medimmune Way, Gaithersburg , MD 20878-2204 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do-Youn","family":"Oh","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, and Cancer Research Institute, Seoul National University College of Medicine , 103, Daehak-ro, Jongno-gu, Seoul 110-744 ,","place":["South 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