{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:11:00Z","timestamp":1789657860172,"version":"4.0.1"},"reference-count":7,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"\n Importance<\/jats:title>\n In the TOPAZ-1 trial\u2019s primary analysis, durvalumab plus gemcitabine and cisplatin (GemCis) showed statistically significant improved overall survival (OS) vs placebo plus GemCis with comparable safety between treatment groups in participants with advanced biliary tract cancer (aBTC). Durvalumab plus GemCis was recently established as the first-line standard of care among patients with aBTC.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate 4-year OS and safety of durvalumab plus GemCis in participants with aBTC.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This post hoc analysis of the global, double-blind, placebo-controlled, phase 3 TOPAZ-1 randomized clinical trial included participants 18 years and older with histologically confirmed unresectable, locally advanced, or metastatic biliary tract adenocarcinoma. In the TOPAZ-1 trial, patients were enrolled from April 2019 to December 2020 at 105 sites in 17 countries. Data cutoff was February 28, 2025.<\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n \n Participants received intravenous durvalumab, 1500 mg, or placebo plus gemcitabine, 1000 mg\/m\n 2<\/jats:sup>\n , and cisplatin, 25 mg\/m\n 2<\/jats:sup>\n , on days 1 and 8 every 3 weeks for up to 8 cycles, followed by durvalumab or placebo monotherapy every 4 weeks.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n OS, duration of treatment exposure, serious adverse events, and adverse events resulting in discontinuation were assessed approximately 48 months after the last participant was randomized.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Overall, 685 participants were randomized, with 341 receiving durvalumab plus GemCis (median [range] age, 64 [20-84] years; 172 [50.4%] female) and 344 receiving placebo plus GemCis (median [range] age, 64 [31-85] years; 168 [48.8%] female). Median (range) follow-up in censored participants was 56.9 (1.7-67.2) months for participants who received durvalumab plus GemCis and 50.7 (0.9-62.6) months for participants who received placebo plus GemCis. Median OS was 13.0 (95% CI, 11.6-14.1) months for durvalumab plus GemCis and 11.4 (95% CI, 10.1-12.5) months for placebo plus GemCis (hazard ratio, 0.75; 95% CI, 0.64-0.88); 48-month OS rate was 11.8% vs 4.3%, respectively. The rate of serious adverse events possibly related to treatment was similar between arms (52 of 338 participants [15.4%] in the durvalumab plus GemCis arm vs 59 of 342 participants [17.3%] in the placebo plus GemCis arm). In the durvalumab plus GemCis and placebo plus GemCis arms, 21 of 338 participants (6.2%) and 18 of 342 participants (5.3%), respectively, experienced adverse events leading to study drug discontinuation.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this post hoc analysis of the phase 3 TOPAZ-1 randomized clinical trial, durvalumab plus GemCis demonstrated long-term survival benefit and a clinically manageable safety profile, supporting its use as a first-line treatment for aBTC.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT03875235<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoncol.2026.2204","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T15:00:24Z","timestamp":1783609224000},"page":"960","source":"Crossref","is-referenced-by-count":3,"title":["Durvalumab Plus Chemotherapy for Advanced Biliary Tract Cancer"],"prefix":"10.1001","volume":"12","author":[{"given":"Do-Youn","family":"Oh","sequence":"first","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiwu Ruth","family":"He","sequence":"additional","affiliation":[{"name":"Herbert Irving Comprehensive Cancer Center, New York-Presbyterian\/Columbia University Irving Medical Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shukui","family":"Qin","sequence":"additional","affiliation":[{"name":"Cancer Center of Nanjing, Jinling Hospital, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Tzong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kaohsiung Medical University Hospital, Center for Cancer Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan"},{"name":"National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuji","family":"Okusaka","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Griffin","sequence":"additional","affiliation":[{"name":"Oncology Biometrics, Late Oncology Statistics, AstraZeneca, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Wang","sequence":"additional","affiliation":[{"name":"Oncology R&D, Late-Stage Development, AstraZeneca, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Xynos","sequence":"additional","affiliation":[{"name":"Oncology R&D, Late-Stage Development, AstraZeneca, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt","family":"Vogel","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Toronto General Hospital, Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada"},{"name":"Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan W.","family":"Valle","sequence":"additional","affiliation":[{"name":"Cholangiocarcinoma Foundation, Herriman, Utah"},{"name":"Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"2","key":"coi260033r1","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.annonc.2022.10.506","article-title":"Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.","volume":"34","author":"Vogel","year":"2023","journal-title":"Ann Oncol"},{"issue":"8","key":"coi260033r2","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2200015","article-title":"Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer.","volume":"1","author":"Oh","year":"2022","journal-title":"NEJM Evid"},{"issue":"5","key":"coi260033r3","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1016\/S1470-2045(24)00082-2","article-title":"Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial.","volume":"25","author":"Burris","year":"2024","journal-title":"Lancet Oncol"},{"issue":"8","key":"coi260033r4","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1016\/S2468-1253(24)00095-5","article-title":"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.","volume":"9","author":"Oh","year":"2024","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"5","key":"coi260033r5","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1016\/j.jhep.2025.05.003","article-title":"Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study.","volume":"83","author":"Oh","year":"2025","journal-title":"J Hepatol"},{"issue":"1","key":"coi260033r6","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2024.104003","article-title":"ESMO Clinical Practice Guideline interim update on the management of biliary tract cancer.","volume":"10","author":"Vogel","year":"2025","journal-title":"ESMO Open"},{"issue":"16","key":"coi260033r7","doi-asserted-by":"publisher","first-page":"4093","DOI":"10.1200\/JCO.2024.42.16_suppl.4093","article-title":"Three-year follow-up data from KEYNOTE-966: pembrolizumab (pembro) plus gemcitabine and cisplatin (gem\/cis) compared with gem\/cis alone for patients (pts) with advanced biliary tract cancer (BTC).","volume":"42","author":"Finn","year":"2024","journal-title":"J Clin Oncol"}],"container-title":["JAMA Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/articlepdf\/2851484\/jamaoncology_oh_2026_oi_260033_1789560632.46179.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:01:05Z","timestamp":1789657265000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/fullarticle\/2851484"}},"subtitle":["A Post Hoc Analysis of the TOPAZ-1 Randomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":7,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaoncol.2026.2204","relation":{},"ISSN":["2374-2437"],"issn-type":[{"value":"2374-2437","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9,1]]}}}