EGFR and head and neck squamous cell carcinoma: Moreover, most of the second-line trials in R/M SCCHN have traditionally allowed any number of prior therapies for R/M disease and, therefore, in these trials, “second-line” therapy implies “second-line and beyond.” Although not the principal focus of this review manuscript, we will also briefly discuss recent observations involving kinase inhibitors such as afatinib (a pan-human EGFR inhibitor, which blocks tyrosine kinase function in human EGFR 1, 2, and 4) and buparlisib [targeting phosphoinositol-3-kinase (PI3K)].