{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:29:59Z","timestamp":1783524599816,"version":"3.55.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Cadonilimab, a bispecific antibody targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), was the first agent of its class to demonstrate promising therapeutic efficacy in combination with chemotherapy for patients diagnosed with advanced gastric or gastroesophageal junction adenocarcinoma (GC\/GEJC). This economic evaluation aimed to determine whether cadonilimab plus chemotherapy offers cost-effective benefits compared to chemotherapy alone from both the U.S. and Chinese healthcare payer perspectives. In addition, we estimated the pricing thresholds at which cadonilimab would be considered economically viable as a first-line treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We constructed a Markov model comprising three health states, progression-free survival (PFS), progressive disease (PD), and death, spanning a 10-year time horizon. The clinical efficacy data were sourced from the randomized phase 3 COMPASSION-15 trial. The cost and utility parameters were derived from existing literature. The model calculates total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Subgroup, scenario, and sensitivity analyses were performed, and price simulations explored cost-effective thresholds at defined willingness-to-pay (WTP) levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the base-case analysis, the cadonilimab plus chemotherapy provided an incremental gain of 0.33 QALYs at an additional cost of $16,797.61, resulting in an ICER of $50,582.10 per QALY, above the WTP threshold of China of $40,354.27 per QALY. In the U.S. setting, although the combination therapy achieved a slightly higher incremental QALY gain of 0.35 QALYs, the substantial additional cost of $101,275.06 resulted in an unfavorable ICER of $290,498.45 per QALY, exceeding the U.S. WTP threshold of $150,000.00. Among Chinese patients with a PD-L1 combined positive score (CPS) \u22655, the ICER was lower at $37,499.27\/QALY, rendering the therapy cost-effective. Simulations identified cadonilimab pricing below $209.54\/125 mg (China) and $826.46\/125 mg (the U.S.) as necessary for cost-effectiveness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Cadonilimab combined with chemotherapy may be cost-effective in Chinese patients with elevated PD-L1 expression. However, its broader use in other patient subgroups or countries requires significant price reductions. These findings provide important guidance for future reimbursements and pricing decisions.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1618726","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T16:27:54Z","timestamp":1760459274000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Cost-effectiveness of cadonilimab plus chemotherapy vs chemotherapy alone for advanced gastric cancer: evidence to inform drug pricing in the U.S. and China"],"prefix":"10.3389","volume":"16","author":[{"given":"Wenwang","family":"Lang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuyong","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zujin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqing","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianling","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(20)31288-5","article-title":"Gastric cancer","volume":"396","author":"Smyth","year":"2020","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"B3","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.jncc.2024.01.006","article-title":"Cancer incidence and mortality in China, 2022","volume":"4","author":"Han","year":"2024","journal-title":"J Natl Cancer Cent"},{"key":"B4","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3322\/caac.21871","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J Clin"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s10120-014-0402-y","article-title":"Her2 screening data from toga: targeting her2 in gastric and gastroesophageal junction cancer","volume":"18","author":"Van Cutsem","year":"2015","journal-title":"Gastric Cancer"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i19.4619","article-title":"Her2 testing in gastric cancer: an update","volume":"22","author":"Abrahao-MaChado","year":"2016","journal-title":"World J Gastroenterol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(23)00515-6","article-title":"Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for her2-negative advanced gastric cancer (Keynote-859): A multicentre, randomised, double-blind, phase 3 trial","volume":"24","author":"Rha","year":"2023","journal-title":"Lancet Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2023-078876","article-title":"Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: rationale-305 randomised, double blind, phase 3 trial","volume":"385","author":"Qiu","year":"2024","journal-title":"Bmj"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.28463","article-title":"First-line sugemalimab plus chemotherapy for advanced gastric cancer: the gemstone-303 randomized clinical trial","volume":"333","author":"Zhang","year":"2025","journal-title":"Jama"},{"key":"B10","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/s0140-6736(21)00797-2","article-title":"First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (Checkmate 649): A randomised, open-label, phase 3 trial","volume":"398","author":"Janjigian","year":"2021","journal-title":"Lancet"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.19918","article-title":"Sintilimab plus chemotherapy for unresectable gastric or gastroesophageal junction cancer: the orient-16 randomized clinical trial","volume":"330","author":"Xu","year":"2023","journal-title":"Jama"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2023.2180794","article-title":"Cadonilimab, a tetravalent pd-1\/ctla-4 bispecific antibody with trans-binding and enhanced target binding avidity","volume":"15","author":"Pang","year":"2023","journal-title":"MAbs"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(23)00411-4","article-title":"Safety and antitumour activity of cadonilimab, an anti-pd-1\/ctla-4 bispecific antibody, for patients with advanced solid tumours (Compassion-03): A multicentre, open-label, phase 1b\/2 trial","volume":"24","author":"Gao","year":"2023","journal-title":"Lancet Oncol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03007-5","article-title":"Cadonilimab with chemotherapy in her2-negative gastric or gastroesophageal junction adenocarcinoma: the phase 1b\/2 compassion-04 trial","volume":"30","author":"Gao","year":"2024","journal-title":"Nat Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03450-4","article-title":"First-line cadonilimab plus chemotherapy in her2-negative advanced gastric or gastroesophageal junction adenocarcinoma: A randomized, double-blind, phase 3 trial","volume":"31","author":"Shen","year":"2025","journal-title":"Nat Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2025.0022","article-title":"Gastric cancer, version 2.2025, nccn clinical practice guidelines in oncology","volume":"23","author":"Ajani","year":"2025","journal-title":"J Natl Compr Canc Netw"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2022.01.011","article-title":"Consolidated health economic evaluation reporting standards 2022 (Cheers 2022) statement: updated reporting guidance for health economic evaluations","volume":"44","author":"Husereau","year":"2022","journal-title":"Clin Ther"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12516","article-title":"The chinese society of clinical oncology (Csco): clinical guidelines for the diagnosis and treatment of gastric cancer, 2023","volume":"44","author":"Wang","year":"2024","journal-title":"Cancer Commun (Lond)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.01357","article-title":"Adjuvant chemoradiotherapy for gastric cancer: efficacy and cost-effectiveness analysis","volume":"9","author":"Zhang","year":"2019","journal-title":"Front Oncol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-14-984","article-title":"Cost-effectiveness analysis of adjuvant chemotherapies in patients presenting with gastric cancer after D2 gastrectomy","volume":"14","author":"Wu","year":"2014","journal-title":"BMC Cancer"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1092385","article-title":"Cost-effectiveness of sintilimab plus chemotherapy versus chemotherapy alone as first-line treatment of locally advanced or metastatic oesophageal squamous cell carcinoma","volume":"14","author":"Liu","year":"2023","journal-title":"Front Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1177\/17562848231207200","article-title":"Immune checkpoint inhibitors plus chemotherapy for her2-negative advanced gastric\/gastroesophageal junction cancer: A cost-effectiveness analysis","volume":"16","author":"Zhu","year":"2023","journal-title":"Therap Adv Gastroenterol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1080\/14737167.2022.2079498","article-title":"Cost-effectiveness analysis of donafenib versus lenvatinib for first-line treatment of unresectable or metastatic hepatocellular carcinoma","volume":"22","author":"Meng","year":"2022","journal-title":"Expert Rev Pharmacoecon Outcomes Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2011.390","article-title":"Cost-effectiveness analysis of trastuzumab to treat her2-positive advanced gastric cancer based on the randomised toga trial","volume":"105","author":"Shiroiwa","year":"2011","journal-title":"Br J Cancer"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.0734","article-title":"Us health care spending by payer and health condition, 1996-2016","volume":"323","author":"Dieleman","year":"2020","journal-title":"Jama"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.0037","article-title":"Cost-effectiveness of atezolizumab plus bevacizumab vs sorafenib as first-line treatment of unresectable hepatocellular carcinoma","volume":"4","author":"Su","year":"2021","journal-title":"JAMA Netw Open"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.vhri.2020.07.580","article-title":"Current development and practice of pharmacoeconomic evaluation guidelines for universal health coverage in China","volume":"24","author":"Yue","year":"2021","journal-title":"Value Health Reg Issues"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-023-00586-6","article-title":"Serplulimab plus chemotherapy vs chemotherapy for treatment of us and chinese patients with extensive-stage small-cell lung cancer: A cost-effectiveness analysis to inform drug pricing","volume":"37","author":"Shao","year":"2023","journal-title":"BioDrugs"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1099-1050(200004)9:3<235::aid-hec502>3.0.co;2-o","article-title":"Development of who guidelines on generalized cost-effectiveness analysis","volume":"9","author":"Murray","year":"2000","journal-title":"Health Econ"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1177\/0272989x12472398","article-title":"Survival analysis for economic evaluations alongside clinical trials\u2013extrapolation with patient-level data: inconsistencies, limitations, and a practical guide","volume":"33","author":"Latimer","year":"2013","journal-title":"Med Decis Making"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-018-0302-8","article-title":"Assessment of proportional hazard assumption in aggregate data: A systematic review on statistical methodology in clinical trials using time-to-event endpoint","volume":"119","author":"Rulli","year":"2018","journal-title":"Br J Cancer"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s40273-022-01227-6","article-title":"Cost-effectiveness analysis of a new second-line treatment regimen for advanced intrahepatic cholangiocarcinoma: biomarker-driven targeted therapy of pemigatinib versus 5-fu chemotherapy","volume":"41","author":"Chueh","year":"2023","journal-title":"Pharmacoeconomics"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1461571","article-title":"Cost-effectiveness analysis of tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced gastric or gastroesophageal junction adenocarcinoma: perspectives from the United States and China","volume":"15","author":"Lang","year":"2024","journal-title":"Front Pharmacol"},{"key":"B34","unstructured":"Medicare Physician Fee Schedule Look-up Tool: Centers for Medicare and Medicaid Services\n          \n          \n          \n          2025"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0196007","article-title":"Assessment of costs associated with adverse events in patients with cancer","volume":"13","author":"Wong","year":"2018","journal-title":"PLoS One"},{"key":"B36","doi-asserted-by":"publisher","first-page":"Epub 20250216","DOI":"10.3390\/curroncol32020112","article-title":"Immunotherapy combined with chemotherapy in the first-line treatment of advanced gastric cancer: systematic review and bayesian network meta-analysis based on specific pd-L1 cps","volume":"32","author":"Zhang","year":"2025","journal-title":"Curr Oncol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1007\/s11096-021-01372-6","article-title":"Cost-effectiveness analysis of nivolumab plus standard chemotherapy versus chemotherapy alone for the first-line treatment of unresectable advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma","volume":"44","author":"Jiang","year":"2022","journal-title":"Int J Clin Pharm"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.6389","article-title":"Pembrolizumab alone or in combination with chemotherapy versus chemotherapy for advanced gastric cancer: A cost-effectiveness analysis","volume":"12","author":"Lang","year":"2023","journal-title":"Cancer Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1080\/14737167.2024.2378983","article-title":"Cost-effectiveness analysis of pembrolizumab plus chemotherapy versus placebo plus chemotherapy for her2-negative advanced gastric\/gastroesophageal junction cancer in the chinese healthcare system","volume":"24","author":"Lang","year":"2024","journal-title":"Expert Rev Pharmacoecon Outcomes Res"},{"key":"B40","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1080\/17474124.2024.2373730","article-title":"Cost-effectiveness of tislelizumab plus chemotherapy vs chemotherapy as first-line treatment of pd-L1 positive advanced gastric or gastroesophageal junction adenocarcinoma from a chinese perspective","volume":"18","author":"Li","year":"2024","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2025.1620663","article-title":"Cost-effectiveness analysis of sugemalimab combined with chemotherapy as first-line treatment for advanced gastric cancer","volume":"13","author":"Tang","year":"2025","journal-title":"Front Public Health"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1477722","article-title":"Updated cost-effectiveness analysis of tislelizumab in combination with chemotherapy for the first-line treatment of advanced gastric cancer or gastroesophageal junction adenocarcinoma","volume":"14","author":"Xu","year":"2024","journal-title":"Front Oncol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1411571","article-title":"Cost-effectiveness analysis of first-line sintilimab plus chemotherapy vs. Chemotherapy alone for unresectable advanced or metastatic gastric or gastroesophageal junction cancer in China","volume":"15","author":"Xiang","year":"2024","journal-title":"Front Pharmacol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1080\/14737167.2024.2378986","article-title":"Pembrolizumab combined with chemotherapy versus placebo combined with chemotherapy for her2-negative advanced gastric cancer in China: A cost-effectiveness analysis","volume":"24","author":"Zheng","year":"2024","journal-title":"Expert Rev Pharmacoecon Outcomes Res"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1177\/17588359231171038","article-title":"First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma: A cost-effectiveness analysis","volume":"15","author":"Cao","year":"2023","journal-title":"Ther Adv Med Oncol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1080\/14737167.2023.2219448","article-title":"Cost-effectiveness analysis of nivolumab-chemotherapy as first-line therapy for locally advanced\/metastatic gastric cancer: A United States payer perspective","volume":"23","author":"Marupuru","year":"2023","journal-title":"Expert Rev Pharmacoecon Outcomes Res"},{"key":"B47","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s12962-023-00476-2","article-title":"Nivolumab plus chemotherapy versus chemotherapy alone as first-line treatment for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: A cost-effectiveness analysis","volume":"21","author":"Zhang","year":"2023","journal-title":"Cost Eff Resour Alloc"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1618726\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T16:27:55Z","timestamp":1760459275000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1618726\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,14]]},"references-count":47,"alternative-id":["10.3389\/fimmu.2025.1618726"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1618726","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,14]]},"article-number":"1618726"}}