Head and Neck Cancer: From Immunotherapy Treatments to New Drug Combinations

Dear Colleagues,

Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer mortality worldwide. Most patients diagnosed with head and neck squamous cell carcinoma (HNSCC) will have locally advanced disease requiring multimodality therapy. Although this approach has curative intent, a significant subgroup of these patients will develop locoregional recurrence and/or distant metastasis, whose prognosis for advanced HNSCC remains poor. Just as immune checkpoint inhibitors (ICIs) have revolutionized treatment in numerous solid tumors, the advent of immunotherapy has produced significant changes in the treatment of head and neck squamous cell carcinoma (HNSCC). This Special Issue, “ Head and Neck Cancer: From Immunotherapy Treatments to New Drug Combinations”, provides a comprehensive overview of the biological rationale and current combination strategies of approved ICIs with chemotherapy and targeted therapy in HNSCC, as well as emerging research and innovative techniques and new combinations with other drugs that could significantly benefit the survival of these patients.

Only 10 years after the approval of cetuximab, the first drugs to show survival benefit for the treatment of relapsed/metastatic HNSCC were anti-PD1/PD-L1 checkpoint inhibitors. The first anti-programmed death-1 (PD-1) immune checkpoint inhibitor to be approved was nivolumab, in patients with recurrent or metastatic HNSCC with disease progression during or after platinum-containing chemotherapy, and, subsequently, pembrolizumab was approved for first-line treatment (either as monotherapy or in combination with chemotherapy).

It has been widely demonstrated that both the innate and adaptive immune systems play a fundamental role in modulating anti-tumor responses to traditional anti-tumor therapies. The function of immunotherapy is precisely to strengthen the ability of the immune system to attack tumor cells. However, only a subgroup of patients benefits from it, and the response rate is still low. Therefore, it appears important to understand the complex interaction between the tumor microenvironment and the genetic alterations that occur within tumor cells. This has led to studies rationalizing a combination of targeted therapy with immunotherapy.

This issue aims to review the most recent completed clinical trials and ongoing studies that aim to improve response rates, prolong response durations, improve safety, help overcome immune checkpoint blockade resistance mechanisms, and increase the possibilities of treatment with the use of immunotherapy and the association of multiple pharmacological therapies. Through this Special Issue, we aim to provide a deeper understanding of the molecular complexities of head and neck squamous cell carcinoma (HNSCC) and highlight the innovations that are driving the advancement of new combinations with anticancer drugs having different mechanisms of delivery action (cytotoxic agents, new molecularly targeted agents, antibody–drug conjugates, immune checkpoint inhibitors, and therapeutic vaccines) and the impact they could have on current therapeutic guidelines.

Dr. Morena Fasano
Guest Editor

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• metastatic head and neck squamous cell carcinoma
• immune checkpoint inhibitors
• targeted therapy
• cytotoxic agents
• tumor microenvironment
• combination strategies