Navigating the challenges of immunotherapy as a neoadjuvant treatment for locally advanced squamous cell carcinoma of the head and neck: A review of the evidence from the literature

Abstract

Locally advanced squamous cell carcinoma of the head and neck (LA-HNSCC) is the most common stage at diagnosis for this disease. Despite significant advancements in cure rates through surgery and chemoradiotherapy, recurrence rates remain high, underscoring the need for alternative strategies to improve outcomes. Immunotherapy, particularly PD-1 inhibitors, has become the standard of care in recurrent or metastatic settings, sparking interest in their use in LA-HNSCC. This review synthesizes the findings of clinical trials investigating neoadjuvant immunotherapy over the past five years, highlighting its potential to improve overall survival and prevent recurrence. We emphasize the substantial heterogeneity of these studies in terms of treatment regimens, combinations, and durations, which complicates the interpretation and comparison of results. Additionally, we discuss the potential role of immunotherapy in tailoring subsequent treatment strategies based on response. We also address key challenges in clinical trial design, such as the selection of appropriate endpoints (e.g., pathological response, toxicity, and time-to-event endpoints like disease-free survival or overall survival) and the integration of biomarkers to predict outcomes. Preliminary findings suggest that adding chemotherapy or other checkpoint inhibitors to PD-1 inhibitors may enhance pathological responses, although further research is needed to determine if this translates into longer survival and improved quality of life. We emphasize the need to identify predictive biomarkers for patient selection and establish consensus in trial design to facilitate result comparisons. In conclusion, while neoadjuvant immunotherapy offers promising opportunities, ongoing research is crucial to refine its clinical application and maximize its therapeutic potential in LA-HNSCC patients.