Current Treatment Options for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Abstract

This review highlights the evidence-based data to support current best management practices for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Current limitations and areas of emerging therapeutics are also emphasized. The cornerstone of palliation for patients with R/M HNSCC is a platinum-based backbone. Platinum doublets induce higher response rates than single agents but do not demonstrate a survival advantage and are associated with increased toxicity. The only regimen to demonstrate survival superiority is platinum, fluorouracil, and cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor (EGFR). EGFR inhibitors, including monoclonal antibodies and tyrosine kinase inhibitors, have achieved only modest success in R/M HNSCC, illustrating the importance of identifying predictive biomarkers and finding ways to overcome mechanisms of resistance. Although phosphoinositide 3-kinase pathway alterations are present at a high rate in HNSCC, the identification of efficacious agents in patients with activating alterations has yet to be discovered. Immunotherapy represents an attractive treatment strategy for R/M HNSCC, with promising preliminary data from studies involving immune checkpoint blockade and toll-like receptor agonists. Human papillomavirus has a prognostic role in R/M disease; therefore, stratification of patients by human papillomavirus status in clinical trials is indicated. Although under-represented in clinical trials, elderly patients experience similar survival outcomes compared with younger patients, albeit with increased toxicity. Despite therapeutic advances, prognosis nonetheless remains poor for patients with R/M HNSCC. Enrollment of patients onto clinical trials to investigate novel therapeutics and identify predictive biomarkers is necessary to further refine and improve outcomes.

Oral mucosal changes induced by anticancer targeted therapies and immune checkpoint inhibitors

“…Substantial progress in our understanding of the mechanism of oncogenesis has led to the emergence of numerous targeted anticancer therapies in the last decade [1][2][3][4]. Their therapeutic effects result mostly from the inhibition of specific molecular receptors and intracellular signaling pathways involved in tumor progression.…”

Gene promoter methylation signature predicts survival of head and neck squamous cell carcinoma patients

“…[2][3][4][5][6] Most importantly, patients with HPV-related tumors show an improved treatment outcome justifying the HPV status as one of the most important biomarkers for favorable prognosis in primary and progressed HNSCC. [7][8][9][10][11] Numerous clinical trials have been launched to evaluate different concepts of treatment de-escalation for HPV-positive HNSCC patients with the aim to reduce treatmentrelated toxicity without raising mortality. [12][13][14][15] However, a substantial amount of HNSCC patients with HPV-related tumors still progress and die, and the prevalence as well as the improved therapeutic outcome of HPV-related tumors at sites other than the oropharynx remains questionable.…”

Epidemiology and Molecular Biology of Head and Neck Cancer

“…Although advancements in techniques and delivery as well as in supportive care have improved the quality of life for patients with HNSCC, the risk of regional and distant relapse is still high. Patients with recurrent or metastatic HNSCC present with enhanced morbidity and a poor prognosis; median survival is 10 months [18]. Thus, gaining insight into molecular principles that control the high incidence of local recurrence and distant metastasis will be instrumental for developing more effective and less toxic therapeutic modalities for the management of HNSCC.…”