From the beginning, the pan-HER TKIs were explored, and numerous studies were conducted with different drugs; however, given their non-specificity (against to EGFR/HER2/HER4), the results were only modest and were associated with a high incidence of EGFR-related toxic effects, such and diarrhoea and skin rash [62,63,64,65,66,67,68,70]. This evidence concerns the gene EGFR and Skin rash.