Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study
- PMID: 40381735
- DOI: 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
Abstract
Background & aims: 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, extended long-term survivors (eLTS), and subsequent anticancer therapy 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 were assessed in the full analysis and safety analysis sets, respectively. eLTS outcomes were assessed (full analysis set participants alive ≥30 months after randomisation).
Results: A total of 685 participants were randomised: durvalumab+GemCis (n = 341); placebo+GemCis (n = 344). After a median 41.3 (95% CI 39.3-44.1) months' follow-up in all participants, median OS (95% CI) for durvalumab+GemCis vs. placebo+GemCis was 12.9 (11.6-14.1) vs. 11.3 (10.1-12.5) months (hazard ratio, 0.74 [95% CI 0.63-0.87]); 36-month OS rate was 14.6% vs. 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%) vs. placebo+GemCis (7.6%). Overall, 12.8% were eLTS, with more eLTS in the durvalumab+GemCis (17.0%) vs. placebo+GemCis (8.7%) arms; eLTS included all clinically relevant subgroups. Durvalumab+GemCis improved OS regardless of subsequent anticancer therapy use. In eLTS, serious adverse events were comparable between arms and less frequent than in the full safety analysis set.
Conclusions: Survival benefit and manageable safety continued with durvalumab+GemCis vs. 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.
Impact and implications: Durvalumab plus gemcitabine and cisplatin (GemCis) was approved for use in advanced biliary tract cancer (aBTC) after the primary analysis of the randomised, double-blind, phase III TOPAZ-1 study demonstrated that it significantly improved overall survival (OS) vs. placebo plus GemCis. This update, with analyses of OS and safety, extended long-term survivors, and subsequent anticancer therapy use, took place at a median follow-up of 41.3 months, which, to our knowledge, represents the longest follow-up to date in participants with aBTC. Survival benefit and manageable safety continued with durvalumab plus GemCis, all clinically relevant subgroups were represented in extended long-term survivors, and OS benefit with durvalumab plus GemCis was consistent regardless of subsequent anticancer therapy use. These long-term follow-up results support the standard-of-care status for durvalumab plus GemCis in aBTC, and enable physicians, patients and caregivers to make informed treatment decisions.
Clinical trial registration: ClinicalTrials.gov Identifier: NCT03875235; https://clinicaltrials.gov/study/NCT03875235.
Keywords: Biliary tract neoplasms; Clinical trials; Gallbladder neoplasms; Immunotherapy.
Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.
Conflict of interest statement
Conflict of interest Do-Youn Oh reports receiving consultant fees from, or having an advisory role for, AbbVie, Arcus Biosciences, ASLAN, Astellas, AstraZeneca, Basilea, Bayer, BeiGene, Bristol Myers Squibb/Celgene, Eutilex, Genentech/Roche, Halozyme, Idience, IQVIA, J-Pharma, LG Chem, Merck Serono, Mirati Therapeutics, Moderna, MSD, Novartis, Taiho, Turning Point, Yuhan, and Zymeworks; and research funding from Array, AstraZeneca, BeiGene, Eli Lilly, Handok, MSD, Novartis, and Servier. Aiwu Ruth He reports receiving fees for speakers’ bureau from AstraZeneca, Bristol Myers Squibb, and Eisai; and research funding from AstraZeneca, Genentech, and Merck. Shukui Qin has no interests to declare. Li-Tzong Chen reports receiving consultant fees from, or having an advisory role for, AstraZeneca, MSD, and SynCoreBio; fees for speakers’ bureau from AstraZeneca, Bristol Myers Squibb, CStone, Eli Lilly, HuniLife Biotechnology, Ipsen, Novartis, Ono Pharmaceutical, PharmaEngine, ScinoPharm Taiwan, SynCoreBio, and TTY; research funding from Celgene; and other fees from OBI Pharma (Data and Safety Monitoring Committee Member for clinical trials) and Taivex (Medical Monitoring for Clinical Trials). Takuji Okusaka reports receiving consultant fees from, or having an advisory role for, AstraZeneca, Bayer Yakuhin, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Eli Lilly, Incyte Corporation, Meiji Seika Pharma, Mundipharma Shire, Nihon Servier, Nippon Shinyaku, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Takara Bio, and Takeda Pharmaceutical; fees for speakers’ bureau from AbbVie, AstraZeneca, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Eli Lilly, Nihon Servier, Novartis, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda Pharmaceutical, Teijin Pharma, and Yakult Honsha; and research funding from AstraZeneca, Baxter, Bristol Myers Squibb, Chugai Pharmaceutical, Dainippon Sumitomo, Eisai, Eli Lilly, Kyowa Hakko Kirin, MSD, Novartis, Ono Pharmaceutical, Pfizer, Syneos Health Nano Carrier, and Taiho Pharmaceutical Co. Jin Won Kim reports receiving consultant fees from, or having an advisory role for, AstraZeneca, BeiGene, Beyond Bio, Bristol Myers Squibb/Celgene, Eisai, GC Cell, MSD, Ono pharmaceutical, Sanofi-Aventis, Servier, and TCUBEit; and research funding from Inno.N and Jeil Pharmaceutical. Thatthan Suksombooncharoen reports receiving consultant fees from, or having an advisory role for, AstraZeneca, Novartis, and Roche/Genentech; and honoraria from AstraZeneca, Baxter, Bayer, Bristol Myers Squibb, Eli Lilly, Janssen, MSD, Novartis, Pfizer, and Takeda Pharmaceutical. Myung Ah Lee has no conflicts of interest to declare. Masayuki Kitano reports receiving research funding from AbbVie, AstraZeneca, and Takeda Pharmaceutical. Howard A. Burris reports receiving consultant fees from, or having an advisory role for, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, FORMA Therapeutics, GRAIL, Incyte, Novartis, Pfizer, and Vincerx; and research funding from AbbVie, Agios, Arch, ARMO Biosciences, Array BioPharma, Arvinas, AstraZeneca, Bayer, BIND Therapeutics, BioAtla, BioMed Valley, BioTheryx, Boehringer Ingelheim, Bristol Myers Squibb, CALGB, CicloMed, Coordination Pharmaceuticals, CytomX, eFFECTOR Therapeutics, Eli Lilly, EMD Serono, Foundation Medicine, Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Harpoon Therapeutics, Hengrui Therapeutics, Incyte, Infinity Pharmaceuticals, Janssen, Jounce Therapeutics, Kymab, MacroGenics, MedImmune, Merck, Millennium/Takeda Pharmaceuticals, miRNA Therapeutics, Moderna, NGM Biopharmaceuticals, Novartis, Pfizer, Revolution Medicine, Roche/Genentech, Ryvu Therapeutics, Seattle Genetics, Tesaro, TG Therapeutics, Verastem, Vertex Pharmaceuticals, XBiotech, and Zymeworks. Mohamed Bouattour reports receiving consultant fees from, or having an advisory role for, AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Ipsen, MSD, Roche, and Sirtex Medical. Suebpong Tanasanvimon reports receiving fees for speakers’ bureau from Amgen, Bristol Myers Squibb, Eisai, Ipsen, Merck, MSD, Novartis, Pfizer, and Roche; and being a Principal Investigator for Amgen, AstraZeneca, MSD, and Roche. Renata Zaucha reports receiving fees for speakers’ bureau from Bristol Myers Squibb and Novartis; travel expenses from Pierre Fabre; being a Principal Investigator for AstraZeneca, Bristol Myers Squibb, Ipsen, Janssen, and Roche; and being a Writer for Ipsen. Antonio Avallone reports receiving consultant fees from, or having an advisory role for, Amgen, AstraZeneca, Bristol Myers Squibb, Eisai, and MSD; and research funding from Amgen and Bayer. Juan Cundom reports receiving consultant fees from, or having an advisory role for, MSD; and fees for speakers’ bureau from AstraZeneca, Boehringer Ingelheim, Roche, and Takeda. Aleksandra Kuzko is an employee of AstraZeneca. Julie Wang and Ioannis Xynos are employees and shareholders of AstraZeneca. Arndt Vogel reports receiving consultant fees from, or having an advisory role for, Amgen, AstraZeneca, Bayer, Boston Scientific, Boehringer Mannheim, Eisai, Incyte, Ipsen, MSD, Pierre Fabre, Roche, Servier, and Sirtex; fees for speakers’ bureau from Bristol Myers Squibb, Eisai, Imaging Equipment, Incyte, Ipsen, MSD, and Roche; and being on the Steering Committee for BeiGene, Jiangsu Hengrui Medicine, MSD, and Roche. Juan W. Valle reports receiving consultant fees from, or having an advisory role for, Agios, AstraZeneca, Autem, Baxter, Hutchinson Medipharma, Image Equipment, NuCana BioMed, QED, Servier, Sirtex, and Zymeworks; fees for speakers’ bureau from Incyte, Ipsen, and Mylan; and research funding from AstraZeneca and RedX. Please refer to the accompanying ICMJE disclosure forms for further details.
Publication types
MeSH terms
Substances
Associated data
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous
