Neratinib’s side effect profile is well characterized and is based on the large number of patients treated in the neratinib program (> 3000 patients), including randomized data from study 3004. This provides robust monotherapy experience from which considerable understanding of the risks can be ascertained. Diarrhoea is the primary AE observed with neratinib treatment and is the most common AE leading to discontinuation. In study 3004, where no anti-diarrhoeal prophylaxis was used, 95.4% of patients experienced diarrhoea, 39.8% experienced grade 3 diarrhoea, and 16.8% discontinued due diarrhoea.