Afatinib is another irreversible pan-HER TKI that did not obtain great efficacy (ORR 7%, mPFS 15.9 weeks, and mOS 56 weeks) in the NICHE phase II trial that enrolled 13 pre-treated patients with HER2 MUT (Ex20) NSCLC [65], another phase II trial did not report efficacy [66], and the most common AEs were diarrhoea, skin rash, mucositis, and transaminitis [65,66]. This evidence concerns the gene ERBB2 and Skin rash.