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서울대학교 의과대학, 서울대학교병원

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J. Hepatol., May 15 2025, S0168-8278(25)02201-9 | https://doi.org/10.1016/j.jhep.2025.05.003 Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study

Do-Youn Oh ^a,b, Aiwu Ruth He ^c, Shukui Qin ^d, Li-Tzong Chen^e,f,g, Takuji Okusaka ^h, Jin Won Kim ⁱ, Thatthan Suksombooncharoen ^j, Myung Ah Lee ^k, Masayuki Kitano ^l, Howard A. Burris^m, Mohamed Bouattour ⁿ, Suebpong Tanasanvimon ^o, Renata Zaucha ^p, Antonio Avallone ^q, Juan Cundom ^r, Aleksandra Kuzko ^s, Julie Wang ^t, Ioannis Xynos ^u, Arndt Vogel ^v,w,x, Juan W. Valle^y,z

^aDivision of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
^bCancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
^cDivision of Hematology and Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USA
^dCancer Center of Nanjing, Jinling Hospital, Nanjing, China
^eKaohsiung Medical University Hospital and Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
^fNational Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
^gNational Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
^hDepartment of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
ⁱMedical Oncology, Seoul National University Bundang Hospital, Seoul, Republic of Korea
^jDepartment of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
^kSeoul St. Mary’s Hospital, College of Medicine, Cancer Research Institute, The Catholic University of Korea, Seoul, Republic of Korea
^lSecond Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
^mDrug Development Department, Sarah Cannon Research Institute, Nashville, Tennessee, USA
ⁿMedical Oncology, AP-HP Hôpital Beaujon, Paris, France
^oFaculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
^pDepartment of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland
^qIstituto Nazionale Tumori-IRCCS Fondazione G. Pascale, Naples, Italy
^rMedical Oncology, Instituto de Investigaciones Metabólicas, Buenos Aires, Argentina
^sOncology R&D, AstraZeneca, Warsaw, Poland
^tOncology R&D, AstraZeneca, New York, USA
^uOncology R&D, AstraZeneca, Cambridge, UK
^vToronto General Hospital, University Health Network, Toronto, Ontario, Canada
^wPrincess Margaret Cancer Centre, Toronto, Ontario, Canada
^xMedical School Hannover, Hannover, Germany
^yResearch, Cholangiocarcinoma Foundation, Herriman, Utah, USA
^zDivision of Cancer Sciences, University of Manchester, Manchester, UK

Corresponding author: Do-Youn Oh

Abstract

Background: At the TOPAZ-1 (NCT03875235) primary analysis, durvalumab plus gemcitabine and cisplatin (GemCis) significantly improved overall survival (OS) in advanced biliary tract cancer (aBTC). We report updated exploratory analyses of OS and safety, characterisation of extended long-term survivors (eLTS), and subsequent anticancer therapy (SAT) use.

Methods: Participants with aBTC received durvalumab+GemCis or placebo+GemCis every 3 weeks (≤8 cycles), then durvalumab or placebo monotherapy every 4 weeks until progressive disease or other discontinuation criteria were met. OS and serious adverse events (SAEs) were assessed in the full analysis and safety analysis sets (FAS/SAS), respectively. eLTS outcomes were assessed (FAS participants alive ≥30 months after randomisation).

Results: 685 participants were randomised: durvalumab+GemCis (n = 341); placebo+GemCis (n = 344). After a median 41.3 (95% confidence interval [CI] 39.3-44.1) months' follow-up in all participants, median OS (95% CI) for durvalumab+GemCis versus placebo+GemCis was 12.9 (11.6-14.1) versus 11.3 (10.1-12.5) months (hazard ratio, 0.74 [95% CI 0.63-0.87]); 36-month OS rate was 14.6% versus 6.9%, respectively. In participants who achieved disease control (566/685; 82.6%), the 36-month OS rate was higher for durvalumab+GemCis (17.0%) versus placebo+GemCis (7.6%). Overall, 12.8% were eLTS, with more eLTS in the durvalumab+GemCis (17.0%) versus placebo+GemCis (8.7%) arms; eLTS included all clinically relevant subgroups. Durvalumab+GemCis improved OS regardless of SAT use. In eLTS, SAEs were comparable between arms and less frequent than in the full SAS.

Conclusions: Survival benefit and manageable safety continued with durvalumab+GemCis versus placebo+GemCis approximately 3 years after the last participant was randomised. All clinically relevant subgroups were represented in eLTS, supporting standard-of-care status for durvalumab+GemCis in aBTC.

Lay summary: The TOPAZ-1 study found that treatment with durvalumab plus gemcitabine and cisplatin (chemotherapy, also known as GemCis), helped people with advanced biliary tract cancer (BTC) to live longer on average than those treated with a placebo plus GemCis. The latest results from TOPAZ-1 showed that these benefits continued for over 3 years in participants treated with durvalumab plus GemCis and side effects continued to be manageable. At an updated analysis, carried out 3 years after the last participant started the study, twice as many participants treated with durvalumab plus GemCis were alive compared to those treated with placebo plus GemCis. Results also showed that the positive effect of durvalumab plus GemCis compared with placebo plus GemCis was not affected by the use of other therapies some participants received after they finished the study treatment. These results continue to support durvalumab plus GemCis as a standard first-line treatment for people with advanced BTC.

논문정보

형식Research article
게재일2025년 05월 (BRIC 등록일 2025-05-19)
연구진국내(교신)+국외 연구진
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