Abstract
With an increased understanding of the tumor biology of squamous cell carcinoma of the head and neck (SCCHN), targeted therapies have found their way into the clinical treatment routines against this entity. Nevertheless, to date platinum-based cytostatic agents remain the first line choice and targeting the epidermal growth factor-receptor (EGFR) with combined cetuximab and radiation therapy remains the only targeted therapy approved in the curative setting. Investigation of immune checkpoint inhibitors (ICI), such as antibodies targeting programmed cell death protein 1 (PD-1) and its ligand PD-L1, resulted in a change of paradigms in oncology and in the first approval of new drugs for treating SCCHN. Nivolumab and pembrolizumab, two anti-PD-1 antibodies, were the first agents shown to improve overall survival for patients with metastatic/recurrent tumors in recent years. Currently, several clinical trials investigate the role of ICI in different therapeutic settings. A robust set of biomarkers will be an inevitable tool for future individualized treatment approaches including radiation dose de-escalation and escalation strategies. This review aims to summarize achieved goals, the current status and future perspectives regarding targeted therapies and ICI in the management of SCCHN.
Highlights
Squamous cell carcinoma of the head and neck (SCCHN) is diagnosed in approximately500,000 patients per year worldwide with rising incidence [1], mainly attributed to younger individuals with Human-Papilloma-Virus (HPV)-positive tumors and to an increasing number of elderly patients due to an improved life expectancy [2]
The approval of the epidermal growth factor-receptor (EGFR) antagonist cetuximab introduced the first targeted therapy in SCCHN showing increased locoregional control when compared to RT alone [7] and improved outcome when combined with chemotherapy in the palliative situation [8]
CONDOR enrolled patients with low/negative PD-L1 tumor expression (TPS < 25%). They were randomized in a 2:1:1 design to either receive durvalumab (20 mg/kg BW q4w) and tremelimumab (IgG2 cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibody, AstraZeneca, 1 mg/kg BW q4w) for 4 cycles followed by durvalumab (10 mg/kg BW q2w), or durvalumab (10 mg/kg BW q2w) monotherapy, or tremelimumab (10 mg/kg BW q4w for 7 doses every 12 weeks for 2 doses) monotherapy
Summary
Squamous cell carcinoma of the head and neck (SCCHN) is diagnosed in approximately. 500,000 patients per year worldwide with rising incidence [1], mainly attributed to younger individuals with Human-Papilloma-Virus (HPV)-positive tumors and to an increasing number of elderly patients due to an improved life expectancy [2]. RT can modulate these effects via “immune vaccination” (e.g., through up-regulation of MHC class I molecules) and enhanced antigen presentation on the surface of tumor and dendritic cells (DC), which may partly explain the abscopal effect occasionally seen in the clinical setting [10]. These observations, together with the encouraging results observed for other malignant diseases [11,12] led to an abundance of clinical trials aiming to modulate immune response for SCCHN, especially regarding immune-checkpoint inhibition (ICI) [13,14,15]. Trials were identified at www.ClinicalTrials.gov, at PubMed database or from presentations at corresponding societal meetings
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