Checkpoint Inhibitors in Head and Neck Cancer: Current Knowledge and Perspectives

Abstract

The emergence of immunotherapy has provided significant clinical improvements in the treatment of metastatic solid tumors. Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) has dismal prognosis with median survival ranging between 6and12 months. Our aim is to review the current knowledge on the role of the immune system and immune checkpoint inhibitors in HNSCC. We will focus on the landmark trials that led to the regulatory approvals of pembrolizumab and nivolumab, and discuss a few promising contenders in clinical development and highlight the need to identify better biomarkers other than programmed death-ligand 1 to improve patient selection and help predict response.

Case of anti-Zic4 antibody-mediated cerebellar toxicity induced by dual checkpoint inhibition in head and neck squamous cell carcinoma

“…The use of combination checkpoint inhibitor therapy with the anti-PD-L1 monoclonal antibody nivolumab and the anti-cytotoxic T-lymphocyte associated protein 4 (anti-CTLA4) monoclonal antibody ipilimumab in the treatment of recurrent or metastatic HNSCC was being investigated in the CheckMate 651 trial, which studied this combination compared with the standard first-line chemotherapy regimen, and had garnered significant interest for its clinical responses; however, data from the trial have not yet been released and this combination had not received approval by the Food and Drug Administration (FDA) for this indication. 3 Nevertheless, after a thorough discussion of the possible adverse effects of first-line combined chemotherapy versus those of dual checkpoint inhibition, the patient opted for dual immunotherapy. In February 2019, he was initiated on off-label dual immune checkpoint inhibition with the anti-PD-L1 monoclonal antibody nivolumab at a dose of 3 mg/kg administered intravenously every 2 weeks with the anti-CTLA4 monoclonal antibody ipilimumab at the low dose of 1 mg/kg administered intravenously every 6 weeks.…”

“…Given the success of immune checkpoint inhibitors in other malignancies, most notably metastatic melanoma and non-small cell lung cancer (NSCLC), some select patients with metastatic HNSCC are currently being treated with dual checkpoint inhibition with nivolumab and ipilimumab as first-line therapy and are being compared with patients receiving the standard of care chemoimmunotherapy regimen. 3 Alongside impressive responses, several immune-related adverse effects (irAEs) have been noted with varying degrees of frequency and severity, and in some cases can be life-threatening or fatal. 4 We present the case of a patient with metastatic p16-positive HNSCC treated with dual checkpoint inhibition with ipilimumab and nivolumab who experienced severe cerebellar ataxia with a positive screen for the anti-Zic4 antibody, which has been associated with cerebellar degeneration in small cell lung cancer (SCLC) and has thus far never been reported in association with HNSCC.…”

Intratumoral generation of 2‐fluoroadenine to treat solid malignancies of the head and neck

“…The approach was safe and well tolerated, without serious adverse events or dose‐limiting toxicity. Greater than 60% overall response rate was obtained in a small number of patients at higher dosing cohorts, and because the best available interventions for end‐stage HNSCC have considerably lower rates of tumor regression (eg, checkpoint blockade inhibitors exhibit overall response rates less than 25% in this setting), FDA has indicated willingness to consider registration if comparably high response rates can be obtained as part of a follow‐on, single‐arm study of individuals with locoregional (needle accessible) HNSCC. This clinical indication has received orphan drug status from FDA, and a pivotal, patient‐oriented trial was recently approved by the agency, with enrollment planned to begin in the first quarter of 2019.…”

Medical Gas Plasma Treatment in Head and Neck Cancer—Challenges and Opportunities

“…In addition, patients often develop loco-regional recurrences, distant metastases, and second primary tumors [55]. The emergence of immunotherapy, especially immune checkpoint inhibitors (ICIs), has provided significant clinical improvements, but only about 20% of the patients respond to this kind of cancer therapy [56]. The prognosis for patients with head and neck cancer is mainly determined by the stage at diagnosis.…”

“…The prognosis for patients with head and neck cancer is mainly determined by the stage at diagnosis. It is devastating to note that survival has not markedly improved in recent decades, with there being an average 5-year survival rate of only 40-50%, and even as poor as 25% for hypopharyngeal cancer [55][56][57]. This highlights the urgent need for new treatment strategies, experimental investigations, and discoveries of new therapeutic targets in HNSCC.…”