The drugs used for second-line treatments of R/M HNSCC targeting the EGFR pathway included anti-EGFR monoclonal antibodies (zalutumumab, cetuximab, vandetanib, and duligotuzumab) and EGFR-TKIs (afatinib and gefitinib) [22,27,35]. This evidence concerns the gene EGFR and head and neck squamous cell carcinoma.