Therapeutic Intensification and Induction Chemotherapy for High-Risk Locally Advanced Squamous Cell Carcinoma

The treatment of HNSCC has rapidly evolved over the past 30 years and multidisciplinary management is required, especially for locally advanced disease (LAHNSCC). Concomitant chemoradiation (cCRT) is the standard of care and cetuximab/RT (CET/RT) is an alternative treatment option, especially for patients unfit for concurrent cisplatin. Several intensification strategies have been explored to improve the outcome of the concomitant treatment. The combination of cisplatin plus cetuximab concurrent to RT failed to improve overall survival (OS) in two phase III trials. Induction chemotherapy (IC) has a proven role in organ preservation; however, its ability in prolonging OS has not been clearly demonstrated. Immune checkpoint inhibitors (ICIs), specifically anti PD-1 inhibitors, have been recently approved for the treatment of patients with recurrent/metastatic platinum-refractory disease. Recent clinical trials are exploring the role of immunotherapy at earlier stages of the disease in combination with concomitant treatments. The purpose of this article is to review current evidence regarding treatment intensification strategies for LAHNSCC (except nasopharyngeal carcinomas) with particular emphasis on the role of induction chemotherapy.