Anti-EGFR enhanced neoadjuvant immunotherapy versus neoadjuvant immunochemotherapy for locally advanced oral squamous cell carcinoma

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.