Novel Immune Oncology Targets Beyond PD-1/PD-L1 in Head and Neck Cancer

Abstract Anti-PD-1 immune checkpoint inhibitors have recently revolutionized the treatment of recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) patients, both in the first and second recurrent and metastatic settings. However, not all patients respond to PD-1 blockade, nor derive prolonged benefit from these immunotherapies, requiring further development of immune-oncology strategies beyond PD-1/PD-L1 inhibitors. There has been an important therapeutic development with the evaluation of many new immune checkpoints molecules and other type of immunomodulatory molecules, along with combinations of these new agents with PD-1/PD-L1 inhibitors, but very few of these strategies have shown significant anti-tumor activity as single agent in HNSCC patients, and further results are awaited from ongoing trials. All randomized trials assessing novel immune-oncology drugs in combination with an anti-PD1/PD-L1 agents have failed so far in HNSCC patients. Many other immune-oncology drugs are still in early clinical development and will hopefully improve HNSCC patient outcomes.