Integrating Immunotherapy into Multimodal Treatment of Head and Neck Cancer

Simple Summary Immune checkpoint inhibitors have become the standard of care therapy in a multimodal setting for recurrent/metastatic HNSCC. Multiple clinical trials have recently looked at the addition of ICI to multimodal treatments in locally advanced HNSCC. Multiple Phase II/III trials are investigating the combination of ICI with definitive chemoradiation. Phase I/II trials have concluded that neoadjuvant ICIs are relatively safe when given prior to surgery and do not generally cause a delay in proceeding to surgery within 4 to 6 weeks. A significant pathological response occurs in about 20% of cases with monotherapy and may be higher with combination therapy. Phase III trials are ongoing to include neoadjuvant immunotherapy along with adjuvant immunotherapy for high-risk features in the postoperative setting along with chemoradiation. Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) have a poor prognosis, with a significant risk of progression or death despite multimodal treatment with surgery, chemotherapy, and radiotherapy. Immune checkpoint inhibitors targeting the programmed death receptor-1 (PD1) have dramatically changed the treatment landscape for recurrent/metastatic disease, improving overall survival in both the first- and second-line palliative settings. This success has driven the investigation of treatment strategies incorporating immunotherapy earlier into the multimodal curative-intent or salvage treatment of both locally advanced and recurrent/metastatic HNSCC. This review encompassed the following three subjects, with a focus on recently reported and ongoing clinical trials: (1) the use of neoadjuvant immunotherapy prior to surgery for locally advanced HNSCC, (2) the use of immunochemoradiotherapy for locally advanced head and neck cancers, and (3) novel uses of immunotherapy in the salvage of recurrent/metastatic HNSCC via a combined modality, including reirradiation paradigms. The results of these studies are eagerly awaited to improve patient outcomes in this challenging disease.