{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T21:22:56Z","timestamp":1785187376071,"version":"3.55.0"},"reference-count":42,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"unspecified","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China postdoctoral science foundation","doi-asserted-by":"crossref","award":["2023M732458"],"award-info":[{"award-number":["2023M732458"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,11,20]]},"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Enfortumab vedotin and pembrolizumab (EV\u2013Pem) have recently been shown to improve the prognosis of patients with untreated locally advanced or metastatic urothelial carcinoma (la\/mUC) in a randomised phase three clinical trial. This study aims to evaluate the cost-effectiveness of EV\u2013Pem as a first-line treatment for patients with la\/mUC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>We developed a three-state Markov model to simulate the treatment pathways for patients with la\/mUC. Costs associated with drugs, treatment monitoring, adverse event management and utility inputs were obtained from national cost databases, trial data and existing literature. In addition to the base-case analysis, sensitivity, threshold and subgroup analyses were performed to assess uncertainty.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>The National Health Service and Personal Social Services perspective.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>A hypothetical English cohort of patients with la\/mUC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>First-line treatment with either EV\u2013Pem or chemotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main outcome measures<\/jats:title>\n                    <jats:p>Costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated over a lifetime horizon as primary outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In patients with la\/mUC, EV\u2013Pem increased health outcomes by 0.82 QALYs (95% uncertainty interval (UI) 0.66 to 0.92) at an incremental cost of \u00a376 793.75 (95% UI 75\u2009759.96 to 77\u2009750.72) versus chemotherapy, yielding an ICER of \u00a393 650.92 per QALY (95% UI \u00a383 471.84 to 116 739.74). One-way sensitivity analysis revealed that factors such as utility values, EV prices and discount rates influence model outcomes, but these variations did not alter the conclusion. Probabilistic sensitivity analysis indicated that, at a willingness-to-pay threshold of \u00a330 000 per QALY, the probability of cost-effectiveness is 0. Results remained robust across subgroup analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this economic model analysis, EV\u2013Pem is not cost-effective compared with first-line chemotherapy in the UK, and a price reduction may be necessary.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-103709","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T09:50:31Z","timestamp":1764928231000},"page":"e103709","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Cost-effectiveness analysis of enfortumab vedotin and pembrolizumab versus chemotherapy for patients with untreated advanced urothelial cancer in the United Kingdom"],"prefix":"10.1136","volume":"15","author":[{"given":"Qiuji","family":"Wu","sequence":"first","affiliation":[{"name":"West China Hospital of Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu","family":"Li","sequence":"additional","affiliation":[{"name":"West China Hospital of Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8190-9442","authenticated-orcid":false,"given":"Yi","family":"Qin","sequence":"additional","affiliation":[{"name":"Sichuan Cancer Hospital and Institute, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"2026010703455231000_15.12.e103709.1","doi-asserted-by":"publisher","DOI":"10.3322\/CAAC.21834"},{"key":"2026010703455231000_15.12.e103709.2","unstructured":"Cancer statistics for the UK. 2024. Available: https:\/\/www.cancerresearchuk.org\/health-professional\/cancer-statistics-for-the-uk [Accessed 10 Oct 2024]."},{"key":"2026010703455231000_15.12.e103709.3","doi-asserted-by":"crossref","first-page":"3881","DOI":"10.1200\/JCO.22.02763","article-title":"Gemcitabine and Cisplatin Versus Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Advanced or Metastatic Bladder Cancer: Results of a Large, Randomized, Multinational, Multicenter, Phase III Study","volume":"41","author":"von der Maase","year":"2023","journal-title":"J Clin Oncol"},{"key":"2026010703455231000_15.12.e103709.4","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1992.10.7.1066"},{"key":"2026010703455231000_15.12.e103709.5","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/s41585-024-00872-0","article-title":"The evolving treatment landscape of metastatic urothelial cancer","volume":"21","author":"Roviello","year":"2024","journal-title":"Nat Rev Urol"},{"key":"2026010703455231000_15.12.e103709.6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.euros.2025.08.009","article-title":"Criteria Used to Determine Platinum Eligibility in Patients with Metastatic Urothelial Carcinoma: Results of a Physician Survey in Five European Countries","volume":"81","author":"Gupta","year":"2025","journal-title":"Eur Urol Open Sci"},{"key":"2026010703455231000_15.12.e103709.7","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30616-2"},{"key":"2026010703455231000_15.12.e103709.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32455-2"},{"key":"2026010703455231000_15.12.e103709.9","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-01963-7"},{"key":"2026010703455231000_15.12.e103709.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.08.016"},{"key":"2026010703455231000_15.12.e103709.11","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.02887"},{"key":"2026010703455231000_15.12.e103709.12","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2312117"},{"key":"2026010703455231000_15.12.e103709.13","unstructured":"FDA approves enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial cancer. 2024. Available: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-enfortumab-vedotin-ejfv-pembrolizumab-locally-advanced-or-metastatic-urothelial-cancer [Accessed 20 Aug 2024]."},{"key":"2026010703455231000_15.12.e103709.14","unstructured":"European Medicines Agency (EMA) . Padcev. 2024. Available: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/padcev [Accessed 10 Oct 2024]."},{"key":"2026010703455231000_15.12.e103709.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.03.001"},{"key":"2026010703455231000_15.12.e103709.16","unstructured":"National comprehensive cancer network . NCCN Clinical Practice Guidelines in oncology, 5 bladder cancer. Version 4. 2024. Available: https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/bladder.pdf [Accessed 10 Oct 2024]."},{"key":"2026010703455231000_15.12.e103709.17","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s13167-010-0050-1","article-title":"Overview of healthcare in the UK","volume":"1","author":"Grosios","year":"2010","journal-title":"EPMA J"},{"key":"2026010703455231000_15.12.e103709.18","unstructured":"NICE health technology evaluations: the manual. Available: https:\/\/www.nice.org.uk\/process\/pmg36 [Accessed 27 Oct 2025]."},{"key":"2026010703455231000_15.12.e103709.19","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1038\/s41416-022-01718-5","article-title":"Differences in cancer incidence by broad ethnic group in England, 2013-2017","volume":"126","author":"Delon","year":"2022","journal-title":"Br J Cancer"},{"key":"2026010703455231000_15.12.e103709.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2023.03.029"},{"key":"2026010703455231000_15.12.e103709.21","unstructured":"National Institute for Health and Care Excellence . Guide to the methods of technology appraisal 2013. NICE. Available: https:\/\/www.nice.org.uk\/process\/pmg9\/resources\/guide-to-the-methods-of-technology-appraisal-2013-pdf-2007975843781 [Accessed 10 Oct 2024]."},{"key":"2026010703455231000_15.12.e103709.22","doi-asserted-by":"publisher","DOI":"10.1017\/S1744133112000096"},{"key":"2026010703455231000_15.12.e103709.23","doi-asserted-by":"crossref","first-page":"S375","DOI":"10.1016\/j.jval.2023.09.1968","article-title":"HTA285 The Impact of the Disease Severity Modifier on NICE Technology Appraisal Decisions","volume":"26","author":"Lee","year":"2023","journal-title":"Value Health"},{"key":"2026010703455231000_15.12.e103709.24","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035807.Epub"},{"key":"2026010703455231000_15.12.e103709.25","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-12-9"},{"key":"2026010703455231000_15.12.e103709.26","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s40425-018-0440-9","article-title":"Cost-effectiveness of nivolumab plus ipilimumab as first-line therapy in advanced renal-cell carcinoma","volume":"6","author":"Wu","year":"2018","journal-title":"J Immunotherapy Cancer"},{"key":"2026010703455231000_15.12.e103709.27","unstructured":"Office for national statistics . National life tables: UK. Available: https:\/\/www.ons.gov.uk\/peoplepopulationandcommunity\/birthsdeathsandmarriages\/lifeexpectancies\/datasets\/nationallifetablesunitedkingdomreferencetables [Accessed 10 Oct 2024]."},{"key":"2026010703455231000_15.12.e103709.28","unstructured":"NHS Digital . Health survey for england, 2022 part 2. Available: https:\/\/digital.nhs.uk\/data-and-information\/publications\/statistical\/health-survey-for-england\/2022-part-2\/adult-overweight-and-obesity [Accessed 10 Oct 2024]."},{"key":"2026010703455231000_15.12.e103709.29","unstructured":"National Institute for Health and Care Excellence . British national formulary. Available: https:\/\/www.nice.org.uk\/bnf-uk-only [Accessed 10 Oct 2024]."},{"key":"2026010703455231000_15.12.e103709.30","unstructured":"PSSRU . Unit costs of health and social care. 2023. Available: https:\/\/www.pssru.ac.uk\/project-pages\/unit-costs\/ [Accessed 10 Oct 2024]."},{"key":"2026010703455231000_15.12.e103709.31","unstructured":"National Institute for Health and Care Excellence . Brigatinib for ALK-positive advanced non-small-cell lung cancer that has not been previously treated with an ALK inhibitor[TA670]. 2021. Available: https:\/\/www.nice.org.uk\/guidance\/ta670"},{"key":"2026010703455231000_15.12.e103709.32","unstructured":"National Institute for Health and Care Excellence . Lorlatinib for untreated ALK-positive advanced non-small-cell lung cancer[TA909]. 2023. Available: https:\/\/www.nice.org.uk\/guidance\/ta909 [Accessed 10 Oct 2024]."},{"key":"2026010703455231000_15.12.e103709.33","unstructured":"National Institute for Health and Care Excellence . Atezolizumab for adjuvant treatment of resected non-small-cell lung cancer[TA823]. 2022. Available: https:\/\/www.nice.org.uk\/guidance\/ta823 [Accessed 10 Oct 2024]."},{"key":"2026010703455231000_15.12.e103709.34","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.1016\/j.clgc.2020.07.006","article-title":"Cost-effectiveness of Pembrolizumab versus Carboplatin-based Chemotherapy as First-line Treatment of PD-L1\u2013positive Locally Advanced or Metastatic Urothelial Carcinoma Ineligible for Cisplatin-based Therapy in the United States","volume":"19","author":"Hale","year":"2021","journal-title":"Clin Genitourin Cancer"},{"key":"2026010703455231000_15.12.e103709.35","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.01213"},{"key":"2026010703455231000_15.12.e103709.36","doi-asserted-by":"publisher","DOI":"10.1097\/00005650-200503000-00003"},{"key":"2026010703455231000_15.12.e103709.37","doi-asserted-by":"crossref","first-page":"e195","DOI":"10.1111\/ajco.12477","article-title":"Health state utilities in non-small cell lung cancer: An international study","volume":"13","author":"Nafees","year":"2017","journal-title":"Asia Pac J Clin Oncol"},{"key":"2026010703455231000_15.12.e103709.38","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.jval.2021.08.009","article-title":"Cost-Effectiveness of Cemiplimab Versus Standard of Care in the United States for First-Line Treatment of Advanced Non-small Cell Lung Cancer With Programmed Death-Ligand 1 Expression \u226550","volume":"25","author":"Kuznik","year":"2022","journal-title":"Value Health"},{"key":"2026010703455231000_15.12.e103709.39","unstructured":"2024 voluntary scheme for branded medicines pricing, access and growth.GOV.UK. Available: https:\/\/www.gov.uk\/government\/publications\/2024-voluntary-scheme-for-branded-medicines-pricing-access-and-growth [Accessed 10 Oct 2024]."},{"key":"2026010703455231000_15.12.e103709.40","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.euo.2024.10.003","article-title":"Cost-effectiveness Analysis in the New Era of Treatment Strategies in Metastatic Urothelial Carcinoma Based on Checkmate-901 and EV302\/Keynote-A39","volume":"8","author":"Rieger","year":"2025","journal-title":"Eur Urol Oncol"},{"key":"2026010703455231000_15.12.e103709.41","doi-asserted-by":"crossref","unstructured":"Li A , Wu M , Xie O , et al . Cost-effectiveness of first-line enfortumab vedotin in addition to pembrolizumab for metastatic urothelial carcinoma in the United States. Front Immunol 2024;15. doi:10.3389\/fimmu.2024.1464092","DOI":"10.3389\/fimmu.2024.1464092"},{"key":"2026010703455231000_15.12.e103709.42","doi-asserted-by":"crossref","unstructured":"You M , Zheng Q , He Y . Enfortumab vedotin plus pembrolizumab as a first-line treatment for advanced urothelial carcinoma: a cost-effectiveness analysis from China based on the EV-302 trial. Front Pharmacol 2024;15. doi:10.3389\/fphar.2024.1412292","DOI":"10.3389\/fphar.2024.1412292"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2025-103709","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T11:46:22Z","timestamp":1767786382000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2025-103709"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":42,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12,5]]},"published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1136\/bmjopen-2025-103709"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2025-103709","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]}}}