한빛사논문
- 조회155
Prof Do-Youn Oh, MD1,2*, Prof Aiwu Ruth He, MD3, Mohamed Bouattour, MD4, Takuji Okusaka, MD5, Prof Shukui Qin, MD6, Prof Li-Tzong Chen, MD7,8,9, Prof Masayuki Kitano, MD10, Choong-kun Lee, MD11, Prof Jin Won Kim, MD12, Prof Ming-Huang Chen, MD13, Prof Thatthan Suksombooncharoen, MD14, Masafumi Ikeda, MD15, Prof Myung Ah Lee, MD16, Prof Jen-Shi Chen, MD17, Prof Piotr Potemski, MD18, Howard A Burris III, MD19, Prof Vikas Ostwal, MD20, Suebpong Tanasanvimon, MD21, Chigusa Morizane, MD5, Renata E Zaucha, MD22, Mairéad G McNamara, MB23, Antonio Avallone, MD24, Juan E Cundom, MD25, Valeriy Breder, MD26, Benjamin Tan, MD27, Satoshi Shimizu, MD28, David Tougeron, MD29, Ludovic Evesque, MD30, Mila Petrova, MD31, David B Zhen, MD32, Roopinder Gillmore, PhD33, Vineet Govinda Gupta, MD34, Prof Farshid Dayyani, MD35, Prof Joon Oh Park, MD36, Gary L Buchschacher Jr, MD37, Felipe Rey, MD38, Hyosung Kim, MSc39, Julie Wang, PharmD40, Claire Morgan, MD41, Nana Rokutanda, MD41, Magdalena Żotkiewicz, MSc42, Arndt Vogel, MD43,44, Juan W Valle, MD45,46
1Division of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
2Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, South Korea
3Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA
4Assistance Publique–Hôpitaux de Paris Hôpital Beaujon, Paris, France
5National Cancer Center Hospital, Tokyo, Japan
6Cancer Center of Nanjing, Jinling Hospital, Nanjing, China
7Kaohsiung Medical University Hospital and Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
8National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
9National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
10Wakayama Medical University, Wakayama, Japan
11Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
12Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea
13Taipei Veterans General Hospital, Taipei City, Taiwan
14Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
15National Cancer Center Hospital East, Kashiwa, Japan
16Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
17Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, Taiwan
18Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland
19Sarah Cannon Research Institute, Nashville, TN, USA
20Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
21Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
22Medical University of Gdańsk, Gdańsk, Poland
23Division of Cancer Sciences, University of Manchester and The Christie NHS Foundation Trust, Manchester, UK
24Istituto Nazionale Tumori-IRCCS Fondazione G Pascale, Naples, Italy
25Instituto de Investigaciones Metabólicas, Buenos Aires, Argentina
26N N Blokhin National Medical Research Center of Oncology, Moscow, Russia
27Washington University School of Medicine, St Louis, MO, USA
28Saitama Cancer Center, Kita-Adachi-Gun, Saitama, Japan
29Poitiers University Hospital, Poitiers, France
30Centre Antoine Lacassagne, Nice, France
31MHAT Nadezhda, Sofia, Bulgaria
32Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA
33Royal Free Hospital, London, UK
34Artemis Hospitals, Gurugram, India
35University of California, Irvine, CA, USA
36Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
37Kaiser Permanente Southern California, Los Angeles Medical Center, Los Angeles, CA, USA
38Centro de Investigación y Desarrollo Oncológico, Clínica CIDO, Temuco, Chile
39AstraZeneca, Osaka, Japan
40AstraZeneca, New York, NY, USA
41AstraZeneca, Gaithersburg, MD, USA
42AstraZeneca, Warsaw, Poland
43Toronto General Hospital, University Health Network and Princess Margaret Cancer Center, Toronto, ON, Canada
44Hannover Medical School, Hannover, Germany
45Division of Cancer Sciences, University of Manchester and The Christie NHS Foundation Trust, Manchester, UK
46Cholangiocarcinoma Foundation, Herriman, UT, USA
*Correspondence
Correspondence to: Dr Do-Youn Oh
Abstract
Background
In the preplanned interim analysis of the TOPAZ-1 study, durvalumab plus gemcitabine–cisplatin significantly improved overall survival versus placebo plus gemcitabine–cisplatin in participants with advanced biliary tract cancer. We aimed to report updated overall survival and safety data from TOPAZ-1 with additional follow-up and data maturity beyond the interim analysis.
Methods
TOPAZ-1 was a phase 3, randomised, double-masked, placebo-controlled, global study done at 105 sites in 17 countries. Participants aged 18 years or older with unresectable, locally advanced, or metastatic biliary tract cancer were randomly assigned (1:1) to durvalumab plus gemcitabine–cisplatin or placebo plus gemcitabine–cisplatin using a computer-generated randomisation scheme, stratified by disease status and primary tumour location. Participants received durvalumab (1500 mg) or placebo on day 1 of each cycle every 3 weeks for up to eight cycles, plus gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) intravenously on days 1 and 8 of each cycle every 3 weeks for up to eight cycles, followed by durvalumab (1500 mg) or placebo monotherapy every 4 weeks until disease progression or other discontinuation criteria were met. Investigators and participants were masked to study treatment. The primary endpoint was overall survival. TOPAZ-1 met its primary endpoint at the preplanned interim analysis, and the study is active but no longer recruiting participants. Updated overall survival and safety data from TOPAZ-1, with additional follow-up (data cutoff Feb 25, 2022) and data maturity beyond the interim analysis, are reported here. Efficacy was assessed in the full analysis set (all randomly assigned participants). Safety was assessed in the safety analysis set (all participants who received at least one dose of study treatment). The TOPAZ-1 study is registered with ClinicalTrials.gov, NCT03875235.
Findings
From April 16, 2019, to Dec 11, 2020, 914 participants were enrolled, 685 of whom were randomly assigned (341 to the durvalumab plus gemcitabine–cisplatin group and 344 to the placebo plus gemcitabine–cisplatin group). 345 (50%) participants were male and 340 (50%) were female. Median follow-up at the updated data cutoff was 23·4 months (95% CI 20·6–25·2) in the durvalumab plus gemcitabine–cisplatin group and 22·4 months (21·4–23·8) in the placebo plus gemcitabine–cisplatin group. At the updated data cutoff, 248 (73%) participants in the durvalumab plus gemcitabine–cisplatin group and 279 (81%) participants in the placebo plus gemcitabine–cisplatin group had died (median overall survival 12·9 months [95% CI 11·6–14·1] vs 11·3 months [10·1–12·5]; hazard ratio 0·76 [95% CI 0·64–0·91]). Kaplan–Meier-estimated 24-month overall survival rates were 23·6% (95% CI 18·7–28·9) in the durvalumab plus gemcitabine–cisplatin group and 11·5% (7·6–16·2) in the placebo plus gemcitabine–cisplatin group. Maximum grade 3 or 4 adverse events occurred in 250 (74%) of 338 participants in the durvalumab plus gemcitabine–cisplatin group and 257 (75%) of 342 in the placebo plus gemcitabine–cisplatin group. The most common maximum grade 3 or 4 treatment-related adverse events were decreased neutrophil count (70 [21%] vs 86 [25%]), anaemia (64 [19%] vs 64 [19%]), and neutropenia (63 [19%] vs 68 [20%]).
Interpretation
Durvalumab plus gemcitabine–cisplatin showed robust and sustained overall survival benefit with no new safety signals. Findings continue to support the regimen as a standard of care for people with untreated, advanced biliary tract cancer.
논문정보
- Research article
- 2024년 05월 (BRIC 등록일 2024-06-04)
- 국내(교신)+국외 연구진
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