Systematic analysis of chemotherapy, immunotherapy, and combination therapy in Head and Neck Squamous Cell Carcinoma (HNSCC) clinical trials: Focusing on overall survival and progression-free survival outcomes

Head and neck squamous cell carcinoma (HNSCC) is a challenging malignancy characterized by poor prognosis, particularly in advanced or metastatic stages. Standard chemotherapy, primarily platinum-based, has long been the cornerstone of treatment for recurrent or metastatic HNSCC, yet its survival benefits remain modest, with significant toxicity. The advent of immunotherapy, specifically immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway, has shifted the treatment paradigm by offering durable responses in a subset of patients, particularly those with biomarker-driven indications. Meanwhile, combination therapy, integrating chemotherapy with immunotherapy or targeted agents, has emerged as a potential strategy to enhance therapeutic efficacy. This review provides a comparative analysis of chemotherapy, immunotherapy, and combination therapy (CICT) based on clinical trial outcomes, focusing on two key metrics: overall survival (OS) and progression-free survival (PFS). While chemotherapy alone typically results in limited survival benefits, immunotherapy has demonstrated significant OS improvements, especially in biomarker-selected populations, though its impact on PFS is less consistent. Combination therapies have shown promise in improving both OS and PFS compared to monotherapies, though they also raise concerns about cumulative toxicity. By evaluating the strengths and limitations of each treatment approach, this review aims to clarify their relative roles in the current and future treatment landscape for HNSCC. It also underscores the importance of ongoing research to refine therapeutic strategies and optimize patient outcomes. • Combo chemo-immunotherapy improves overall survival more than chemo or immunotherapy alone. • Immunotherapy, especially checkpoint inhibitors, may benefit recurrent/metastatic HNSCC patients. • Early combo therapy may lead to better long-term survival outcomes. • Combo therapies boost survival but raise toxicity; future focus should be on minimizing toxicity without reducing efficacy.