Neoadjuvant therapy vs. standard of care in oral cavity squamous cell carcinoma: A meta-analysis.

Abstract

e18069 Background: Historically, locally advanced, resectable oral squamous cell carcinoma was treated with upfront surgery followed by adjuvant therapy. Advances in systemic treatment, particularly immunotherapy, have led to paradigm shifts with current NCCN guidelines now supporting the use of neoadjuvant immunotherapy for selected patients with PD-L1–expressing, locally advanced disease. While multiple individual studies and meta-analyses have compared neoadjuvant therapy to surgery alone; no prior meta-analyses have directly compared neoadjuvant and adjuvant approaches in this population. Methods: Pubmed, Embase, and Scopus were searched for articles written since 2015 comparing disease-free survival and overall survival in patients with locally advanced oral squamous cell carcinoma receiving neoadjuvant therapy (chemotherapy +/-immunotherapy, immunotherapy alone) vs. standard of care. Retrospective cohort studies and randomized control trials (RCT) were analyzed separately with combined hazard ratios. Random effects were used when I² > 50% and fixed-effects models were used when I² ≤ 50%. Results: Out of 561 articles, five met criteria for inclusion in the systematic review; 4 had enough data to be included in the meta-analysis. Two of these were retrospective cohort studies (n=221) and two were RCTs(n=996). In the retrospective cohort studies, neoadjuvant therapy was associated with increased overall survival but not disease-free survival. Heterogeneity between those studies was 0%. RCTs showed no difference in overall survival between neoadjuvant and SOC but had a high level of heterogeneity (81%). Conclusions: Neoadjuvant therapy in OCC consistently trended toward increased progression free-survival and overall survival, with retrospective studies retaining significance for overall survival with a low degree of heterogeneity. Prior meta-analyses limited to neoadjuvant chemotherapy have not demonstrated clear survival benefit. By incorporating broader neoadjuvant strategies, including immune checkpoint inhibition, this analysis identifies a consistent directional signal favoring neoadjuvant approaches. Direct comparisons between neoadjuvant pembrolizumab and adjuvant systemic therapy remain absent, underscoring the need for prospective trials. Disease-free and overall survival in patients with oral cavity squamous cell carcinoma receiving neoadjuvant therapy vs standard of care. Study Type Outcome Hazard Ratio 95% Confidence Interval p-value I² Retrospective Cohort Studies Disease-Free Survival 0.45 0.18-1.12 .087 79.71% Retrospective Cohort Studies Overall Survival 0.26 0.16-0.45 <.001 0% Randomized Control Trials Overall Survival 0.53 0.18-1.53 .24 84.32%