ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicEfficacy of Neoadjuvant Immunotherapy and Analysis of Immunomodulation in Head and Neck Squamous Cell CarcinomaView all articles
Anti-EGFR Enhanced Neoadjuvant Immunotherapy Versus Neoadjuvant Immunochemotherapy for Locally Advanced Oral Squamous Cell Carcinoma
Provisionally accepted
- Henan Cancer Hospital Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
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Background: Immune checkpoint inhibitors have transformed the management of metastatic oral squamous cell carcinoma (OSCC), but their efficacy in the neoadjuvant setting is still under investigation. This study aimed to compare the efficacy and safety of neoadjuvant immunochemotherapy (NAIC), neoadjuvant immunotherapy plus cetuximab (NAI-CTX), and neoadjuvant chemotherapy (NAC) in patients with locally advanced OSCC. Methods: In this retrospective cohort study, 475 patients with stage III-IVA OSCC were stratified into three groups: NAIC (n=265), NAI-CTX (n=46), and NAC (n=164). The primary endpoint was pathologic complete response (pCR). Secondary endpoints included event-free survival (EFS), overall survival (OS), major pathologic response (mPR), and treatment-related toxicity. Results: Pathologic outcomes were significantly superior in the NAIC group. The pCR rates were 30.2% for NAIC, compared to 13.0% for NAI-CTX and 7.3% for NAC (p<0.001). Similarly, mPR rates were 69.8%, 39.1%, and 50.0%, respectively (p<0.001). NAIC also achieved a higher objective response rate (90.6% vs. 71.7% vs. 65.9%, p<0.001) and a near-complete R0 resection rate (98.1% vs. 89.1% vs. 97.0%). Survival analysis revealed 3-year EFS rates of 73.6% (NAIC), 56.5% (NAI-CTX), and 46.3% (NAC) (p<0.0001), with corresponding 3-year OS rates of 78.1%, 63.0%, and 59.1% (p<0.0001). Multivariable analysis confirmed the independent survival benefit of NAIC. Toxicity profiles differed: the NAI-CTX group exhibited more cetuximab-related toxicities, while NAIC was associated with a higher incidence of hypothyroidism. No treatment-related deaths occurred. The efficacy of neoadjuvant therapy was primarily associated with PD-L1 expression levels rather than the number of treatment cycles. Conclusion: NAIC demonstrates superior pathologic responses and survival benefits compared to both NAI-CTX and NAC, establishing it as a highly promising neoadjuvant strategy for locally advanced OSCC.
Keywords: neoadjuvant immunotherapy, cetuximab, Neoadjuvant chemotherapy, oral squamous cell carcinoma, prognosis
Received: 19 Jul 2025; Accepted: 03 Nov 2025.
Copyright: © 2025 Li, Jin, Su, Fang and Du. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wei Du, duweitj@126.com
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