Immunotherapy in Patients with Recurrent and Metastatic Squamous Cell Carcinoma of the Head and Neck

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the most common malignant cancer occurring in the head and neck area, approximately 90% of the cases. Even in the cases of primary radical treatment (surgical, concomitant chemoradiotherapy or radiotherapy alone), local recurrence or distal metastases are often observed. In patients with recurrent disease who are unable to receive radical treatment, the results of palliative chemotherapy are not satisfactory. The breakthrough in the therapy of advanced HNSCC was the approval of cetuximab in combination with chemotherapy in 2008. However, for almost a decade we have seen many negative studies with new treatment approaches including various types of molecules targeting epidermal growth factor receptors or vascular endothelial growth factor receptors, as well as different cytokines or cancer vaccines. Recently two new agents have been approved in the treatment of recurrent or metastatic HNSCC. These are immune-checkpoint inhibitors targeting PD1 (nivolumab and pembrolizumab) expressed mainly on T-cells. However, the results remain unsatisfactory - most of the patients do not respond to the treatment and some of the responding patients develop further progression. Many phase 3 studies are currently ongoing evaluating the efficacy of combinational treatment - anti-CTLA4 with anti-PD1 or anti-PD-L1. Very encouraging results have been shown in early phase studies evaluating the combination of immune-checkpoint inhibitors with tumor microenvironment immunosuppressive inhibitors. Undoubtedly, further research in the field of biomarkers for effective immunotherapy is needed in order to select a group of patients whose will benefit from this therapy, as the treatment is still ineffective in most patients.

The efficacy and safety of combined immune checkpoint inhibitors (nivolumab plus ipilimumab): a systematic review and meta-analysis

“…Combination immunotherapy is based on the use of more than one immunotherapy. It can intervene and regulate multiple processes of the immune response through [30], chemoradiotherapy [31][32][33], and targeted therapy [34,35] by promoting anti-tumor immune response reduce the risk of drug resistance. The combination of immunotherapies is one of the most promising approaches being studied [36].…”

EGOT lncRNA in head and neck squamous cell carcinomas

“…Various treatment strategies have been employed in the past couple of decades but none have been great breakthroughs. Improved clinical outcomes will occur once molecular diagnostics and personalized treatments are determined for the different sub-types of this cancer [3,4]. To date, great effort has been dedicated to the discovery of clinical biomarkers, particularly in oncology, and lncRNAs have been identified as one of the new promising classes of molecules [7,8].…”

“…Tobacco smoking, alcohol consumption and human papillomavirus (HPV) infection are the main causes of these malignancies [1,2]. Some progress has been made towards effectively treating HNSCC, however, it remains largely unsatisfactory because of still high mortality [3,4]. Biomarkers that have been associated with different treatment responses are needed to better combat this deadly disease.…”

The efficacy and safety of combined immune checkpoint inhibitors (nivolumab plus ipilimumab): a systematic review and meta-analysis

“…Combined immunotherapy is based on the use of more than one immunotherapy. It can intervene andregulate multiple processes of immune response through [29], chemoradiotherapy [30][31][32] and targeted therapy [33,34] by promoting anti-tumor immune response reduce the risk of drug resistance. The combination of immunotherapies is one of the most promising approaches being studied [35].…”