Updates in Head and Neck Oncology - Current Knowledge and Future Horizons.

Treatment for head and neck recurrent/metastatic squamous cell carcinoma (HNSCC) with immune checkpoint inhibitors has now become the new therapeutic standard, primarily replacing the EXTREME and TPex protocols that included the EGFR inhibitor Cetuximab and chemotherapy. Even if there are considerable advances in therapeutic results, less than 20% of patients with this stage of the disease survive more than four years. These results demonstrate the need to identify more effective therapies beyond simple PD1/PD-L1 blockade. Antibody-drug conjugates (ADC), vaccines, bispecific kinase inhibitors and fusion proteins involving the modulation of the tumor microenvironment are strategies to be exploited in the future. Also, in locally advanced cancers, the results of combining immunotherapy with chemoradiation treatment did not give the expected results. The use of other therapeutic sequences, including immunotherapy in association with neo-adjuvant chemotherapy, but also the association with mTOR inhibitors are also evaluated in clinical trials. We propose to present some new directions in the therapies of locally advanced relapsed or metastatic HNSCC.