{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:56:18Z","timestamp":1790124978159,"version":"4.0.1"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Gastric Cancer"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Nivolumab plus chemotherapy demonstrated clinically significant improvement in quality-adjusted survival versus chemotherapy alone as first-line treatment for advanced non-HER2-positive gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma (GC\/GEJC\/EAC) in the CheckMate 649 post-hoc quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis at 1-year minimum follow-up. We report Q-TWiST analysis results at 4-year minimum follow-up.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Q-TWiST methodology was applied post-hoc to CheckMate 649 study data from all randomized patients, patients with PD-L1 combined positive score (CPS)\u2009\u2265\u20091, and patients with PD-L1 CPS\u2009\u2265\u20095. Relative Q-TWiST gains\u2009\u2265\u200910% were predefined as clinically important and\u2009\u2265\u200915% as clearly clinically important.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Among all randomized patients, patients with PD-L1 CPS\u2009\u2265\u20091, and patients with PD-L1 CPS\u2009\u2265\u20095, mean (95% CI) absolute Q-TWiST gains of 3.4 (1.8\u20135.1), 4.2 (2.4\u20136.1), and 5.4 (3.0\u20137.7) months with nivolumab plus chemotherapy versus chemotherapy were observed, respectively. These translated to clearly clinically important relative Q-TWiST gains of 20.5%, 26.1%, and 33.4% in each population; relative Q-TWiST gains benefit remained clearly clinically important in all subgroups (15.7%, 20.3%, and 26.4%) after expanding the analysis to include grade 2 adverse events. Greater Q-TWiST gains were observed with nivolumab plus chemotherapy across most subgroups in all randomized patients and patients with PD-L1 CPS\u2009\u2265\u20091 and across all subgroups in patients with PD-L1 CPS\u2009\u2265\u20095.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Clearly clinically important benefit in quality-adjusted survival with first-line nivolumab plus chemotherapy versus chemotherapy was observed across all evaluated PD-L1 CPS expression levels in patients with advanced GC\/GEJC\/EAC from CheckMate 649 with 4-year minimum follow-up.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Trial Registration<\/jats:title>\n            <jats:p>ClinicalTrials.gov identifier, NCT02872116.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s10120-025-01634-6","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T09:22:38Z","timestamp":1752139358000},"page":"935-944","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Q-TWiST analysis of first-line nivolumab plus chemotherapy versus chemotherapy in patients with advanced gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma from CheckMate 649: 4-year follow-up results"],"prefix":"10.1007","volume":"28","clinical-trial-number":[{"clinical-trial-number":"nct02872116","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1352-8915","authenticated-orcid":false,"given":"Daniel","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenying","family":"Quan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marne","family":"Garretson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Chirikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prianka","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Sugarman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"issue":"10294","key":"1634_CR1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S0140-6736(21)00797-2","volume":"398","author":"YY Janjigian","year":"2021","unstructured":"Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, et al. 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. Lancet. 2021;398(10294):27\u201340.","journal-title":"Lancet"},{"issue":"17","key":"1634_CR2","doi-asserted-by":"publisher","first-page":"2012","DOI":"10.1200\/JCO.23.01601","volume":"42","author":"YY Janjigian","year":"2024","unstructured":"Janjigian YY, Ajani JA, Moehler M, Shen L, Garrido M, Gallardo C, et al. First-line nivolumab plus chemotherapy for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 3-year follow-up of the phase III CheckMate 649 trial. J Clin Oncol. 2024;42(17):2012\u201320.","journal-title":"J Clin Oncol"},{"key":"1634_CR3","unstructured":"European Medicines Agency. EMA Regulatory Science to 2025 - Strategic reflection. 2020. Available from: https:\/\/www.ema.europa.eu\/en\/documents\/regulatory-procedural-guideline\/ema-regulatory-science-2025-strategic-reflection_en.pdf."},{"issue":"24","key":"1634_CR4","doi-asserted-by":"publisher","first-page":"2925","DOI":"10.1200\/JCO.2016.68.2518","volume":"34","author":"LE Schnipper","year":"2016","unstructured":"Schnipper LE, Davidson NE, Wollins DS, Blayney DW, Dicker AP, Ganz PA, et al. Updating the American Society of Clinical Oncology Value Framework: revisions and reflections in response to comments received. J Clin Oncol. 2016;34(24):2925\u201334.","journal-title":"J Clin Oncol"},{"issue":"4","key":"1634_CR5","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.annonc.2022.12.004","volume":"34","author":"SF Oosting","year":"2023","unstructured":"Oosting SF, Barriuso J, Bottomley A, Galotti M, Gyawali B, Kiesewetter B, et al. Methodological and reporting standards for quality-of-life data eligible for European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) credit. Ann Oncol. 2023;34(4):431\u20139.","journal-title":"Ann Oncol"},{"issue":"suppl 2","key":"1634_CR6","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1200\/jgo.18.25700","volume":"4","author":"TTX Mai","year":"2018","unstructured":"Mai TTX, Jung CY, Hyunsoon C. Utilization of quality-adjusted time without symptoms or toxicity (Q-TWiST) method in oncology: a systematic review of clinical trials. J Global Oncol. 2018;4(suppl 2):102.","journal-title":"J Global Oncol."},{"issue":"3","key":"1634_CR7","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s10120-023-01372-7","volume":"26","author":"D Lin","year":"2023","unstructured":"Lin D, Nguyen H, Shah R, Qiao Y, Hartman J, Sugarman R. Quality-adjusted time without symptoms or toxicity analysis of nivolumab plus chemotherapy versus chemotherapy alone for the management of previously untreated patients with advanced gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma. Gastric Cancer. 2023;26(3):415\u201324.","journal-title":"Gastric Cancer"},{"issue":"3","key":"1634_CR8","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1007\/s11136-005-1579-7","volume":"15","author":"DA Revicki","year":"2006","unstructured":"Revicki DA, Feeny D, Hunt TL, Cole BF. Analyzing oncology clinical trial data using the Q-TWiST method: clinical importance and sources for health state preference data. Qual Life Res. 2006;15(3):411\u201323.","journal-title":"Qual Life Res"},{"issue":"3","key":"1634_CR9","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1080\/14737167.2018.1434414","volume":"18","author":"CT Solem","year":"2018","unstructured":"Solem CT, Kwon Y, Shah RM, Aly A, Botteman MF. Systematic review and benchmarking of quality-adjusted time without symptoms or toxicity (Q-TWiST) in oncology. Expert Rev Pharmacoecon Outcomes Res. 2018;18(3):245\u201353.","journal-title":"Expert Rev Pharmacoecon Outcomes Res"},{"key":"1634_CR10","doi-asserted-by":"crossref","unstructured":"Shitara K, Moehler M, Ajani JA, Shen L, Garrido M, Gallardo C, et al. Nivolumab plus chemotherapy vs chemotherapy as first-line treatment for advanced gastric cancer\/gastroesophageal junction cancer\/esophageal adenocarcinoma: 4-year follow-up of the CheckMate 649 study. Oral presentation at ASCO-GI; January 18\u201320, 2024; San Francisco, CA and Virtual. Abstract 306.","DOI":"10.1200\/JCO.2024.42.3_suppl.306"},{"key":"1634_CR11","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1038\/s41586-022-04508-4","volume":"603","author":"K Shitara","year":"2022","unstructured":"Shitara K, Ajani JA, Moehler M, Garrido M, Gallardo C, Shen L, et al. Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature. 2022;603:942\u20138.","journal-title":"Nature"}],"container-title":["Gastric Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10120-025-01634-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10120-025-01634-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10120-025-01634-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T01:42:41Z","timestamp":1757209361000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10120-025-01634-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,9]]},"references-count":11,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["1634"],"URL":"https:\/\/doi.org\/10.1007\/s10120-025-01634-6","relation":{},"ISSN":["1436-3291","1436-3305"],"issn-type":[{"value":"1436-3291","type":"print"},{"value":"1436-3305","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,9]]},"assertion":[{"value":"10 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"D. Lin reports consulting or advisory role at AstraZeneca, Agenus, and Exelixis; stock and other ownership interests in BioNano Genomics; and honoraria from AstraZeneca, Agenus, and Exelixis. V. Chirikov reports employment at OPEN Health; and research funding from AstraZeneca and Bristol Myers Squibb\/Celgene. C. Chen reports employment at AstraZeneca; and stock and other ownership interests in Bristol Myers Squibb\/Celgene. P. Singh reports employment at Bristol Myers Squibb. All other authors have no relationships to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}