In HNC clinical trials, reversible EGFR TKIs, such as gefitinib and erlotinib, do not seem to confer a therapeutic benefit either as monotherapy or in combination with radiation treatment, with the response rate of erlotinib estimated at 10–15% in HNSCC patients [223]; on the other hand, multitarget TKIs such as lapatinib (reversible dual EGFR and HER2 TKI), afatinib, and dacomitinib (both irreversible EGFR, HER2, and HER4 pan-HER TKIs) have shown promising results in clinical trials, in terms of improving the objective response rate in patients with HNSCC [216,224,225]. Here, ERBB2 is linked to head and neck squamous cell carcinoma.