Neratinib for the treatment of breast cancer.

INTRODUCTION: Neratinib is an orally available, pan-HER inhibitor with clinical activity in patients with HER2-amplified and HER2-mutated breast cancer. Areas covered: A summary of publically available and relevant clinical data on neratinib. Expert opinion: Neratinib (N) is clearly distinct from lapatinib (L), a difference based on its broad anti-HER effect, its covalent target binding and its toxicity profile. The main toxicity of neratinib is gastro-intestinal and is essentially limited to diarrhea. Although not directly compared with single agent lapatinib, skin toxicity is much less pronounced with N. The direct clinical comparison of N-capecitabine versus L-capecitabine is the subject of the ongoing NALA-trial. In patients with advanced disease, neratinib has clinically relevant activity in patients with trastuzumab(T)-pretreated and unpretreated disease. In patients having completed one year of adjuvant trastuzumab, an additional year of neratinib further reduces the risk of recurrence of invasive disease. The activity of neratinib in HER2-mutated advanced disease is subject of ongoing clinical trials but preclinical and early clinical results are promising. Neratinib is a usefull drug and a valuable addition to the different anti-HER2-drugs avalaible for patients with HER2-overexpressing and HER2-mutated breast cancer.