Low-Dose Nivolumab with Induction Chemotherapy Improves Responses and Conversion to Radical Therapy in Locally Advanced/Unresectable HNSCC: An Ambispective Real-world Study

Low-Dose Nivolumab with Induction Chemotherapy Improves Responses and Conversion to Radical Therapy in Locally Advanced/Unresectable HNSCC: An Ambispective Real-world Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Low-Dose Nivolumab with Induction Chemotherapy Improves Responses and Conversion to Radical Therapy in Locally Advanced/Unresectable HNSCC: An Ambispective Real-world Study Josh Thomas Georgy, Soumya Susan Regi, Rosh Varghese Georgy, Balu Krishna Sasidharan, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6388639/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 08 Oct, 2025 Read the published version in Scientific Reports → Version 1 posted 7 You are reading this latest preprint version Abstract Locally advanced head and neck squamous cell carcinoma (LAHNSCC) unresectable at presentation has a dismal survival when radical surgery or definitive chemoradiation is not possible. This ambispective cohort study evaluated the addition of low-dose nivolumab to induction chemotherapy (IC) in patients with locally advanced, unresectable or borderline resectable HNSCC. 111 patients with stage III-IVB disease received IC with low-dose nivolumab (< 240 mg or < 3 mg/kg biweekly). The median nivolumab dose was 0.51 mg/kg biweekly, with a median of 3 doses. Overall response rate per RECIST v1.1 was 75.3% among evaluable patients. 31.6% of oral cavity tumors were rendered resectable, with 32% achieving pathological complete response (pCR). In other sites, the conversion rate to radical chemoradiation was 68.8%. One-year progression-free survival and overall survival were 67% and 83%, respectively, with post-induction radical therapy(p < 0.001) and pCR/rCR (p < 0.01) correlating with significantly longer PFS. Grade ≥ 3 adverse events occurred in 31.5% of patients. The nivolumab cost was reduced by 88.9% relative to standard dosing. These findings of encouraging conversion rate to radical treatment, highlight the potential of chemoimmunotherapy as induction therapy in this cohort with a very poor prognosis, with broader implications of cost savings where access to immune checkpoint inhibitors is limited. Biological sciences/Cancer/Head and neck cancer Biological sciences/Cancer/Head and neck cancer/Oral cancer Biological sciences/Cancer/Cancer therapy/Cancer immunotherapy Biological sciences/Cancer/Cancer therapy/Chemotherapy Biological sciences/Cancer/Cancer therapy/Radiotherapy Unresectable HNSCC Induction Chemotherapy Low-Dose Nivolumab Conversion Cost-Effectiveness Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementaryv1.docx Cite Share Download PDF Status: Published Journal Publication published 08 Oct, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 05 Aug, 2025 Reviews received at journal 23 Jun, 2025 Reviewers agreed at journal 06 May, 2025 Reviewers invited by journal 01 May, 2025 Editor assigned by journal 22 Apr, 2025 Submission checks completed at journal 11 Apr, 2025 First submitted to journal 11 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6388639","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":451660483,"identity":"a15be112-151e-4541-a23d-05118df2b603","order_by":0,"name":"Josh Thomas Georgy","email":"","orcid":"","institution":"Christian Medical College Vellore","correspondingAuthor":false,"prefix":"","firstName":"Josh","middleName":"Thomas","lastName":"Georgy","suffix":""},{"id":451660484,"identity":"befac6ab-fc3b-457f-8ab6-db403356d7b1","order_by":1,"name":"Soumya Susan Regi","email":"","orcid":"","institution":"Christian Medical College 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This ambispective cohort study evaluated the addition of low-dose nivolumab to induction chemotherapy (IC) in patients with locally advanced, unresectable or borderline resectable HNSCC. 111 patients with stage III-IVB disease received IC with low-dose nivolumab (\u0026lt;\u0026thinsp;240 mg or \u0026lt;\u0026thinsp;3 mg/kg biweekly). The median nivolumab dose was 0.51 mg/kg biweekly, with a median of 3 doses. Overall response rate per RECIST v1.1 was 75.3% among evaluable patients. 31.6% of oral cavity tumors were rendered resectable, with 32% achieving pathological complete response (pCR). In other sites, the conversion rate to radical chemoradiation was 68.8%. One-year progression-free survival and overall survival were 67% and 83%, respectively, with post-induction radical therapy(p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and pCR/rCR (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) correlating with significantly longer PFS. Grade\u0026thinsp;\u0026ge;\u0026thinsp;3 adverse events occurred in 31.5% of patients. The nivolumab cost was reduced by 88.9% relative to standard dosing. 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