Immunotherapy in head and neck squamous cell carcinoma: a narrative review
Shay Sharon, R. Bryan Bell
Abstract
Background and Objective: In 2016, two anti-PD1 antibodies, nivolumab and pembrolizumab, were shown to improve overall survival in patients with recurrent/metastatic HNSCC and were approved by the US Food and Drug Administration (FDA) for use in the second line, cisplatin-resistant setting, although the overall response rates were only about 15%. More recently, pembrolizumab was approved for use in the first-line R/M setting as monotherapy in patients with CPS >1 or in combination with chemotherapy regardless of PD-L1 expression. Interestingly, while response rates with combination therapy were increased compared to pembrolizumab alone, the duration of response was shorter than might be expected. Based on a growing amount of evidence in other types of cancer treated with various combinations of immunotherapy, similar concepts are being studied in HNSCC, both in pre-clinical models and in clinical trials. Our objective is to provide a narrative review of the literature describing immunological concepts and novel approaches in the treatment of head and neck squamous cell carcinoma. Methods: A review of the English literature published between January 1st, 1960 and January 2nd, 2021 was conducted using the Medline-PubMed and ClinicalTrials.gov databases. Main topics were selected for review, including basic immunology background, checkpoint inhibition, neoadjuvant immunotherapy, the combination of immunotherapy with radiation therapy and chemotherapy, intratumoral immunotherapy, and future prospects. Key Content and Findings: This review presents recent advancements in treating HNSCC, focusing on the translation of immunological concepts into the standard of care. Key aspects of the immune response are delineated, and their implementation in various treatment modalities is then described. Cancer immunotherapy is a transformational approach for treating HNSCC, but overcoming existing cancer and its future spread poses a significant challenge. Despite the successful application of immunotherapy across multiple tumor types, durable response and cure remain elusive. Large-scale efforts are underway to test novel combinations of immunotherapy with other immunotherapy agents, targeted small molecules, chemotherapy, radiotherapy, and surgery. Future success will depend on better understanding of the synergies between therapies and their effect on the anti-cancer immune response. Providing the appropriate combination for each patient and unveiling the factors that determine a successful outcome is essential to the studies that should follow. Conclusions: There is an ongoing effort, which is supported by an increasing body of evidence, to enhance response rates with combinations of immunotherapy with other immunotherapy agents, targeted small molecules, chemotherapy, radiation therapy, and surgery. The clinician and the scientist should be familiarized with basic immunologic concepts, key findings in recent clinical trials, and current indications for administering immunotherapy.