Neratinib in Early-Stage Breast Cancer: A Profile of Its Use in the EU.

Neratinib (Nerlynx) is an oral, irreversible pan-human epidermal growth factor receptor (HER) tyrosine kinase inhibitor of HER1, HER2 and HER4. Neratinib therapy for 12 months significantly reduced the risk of invasive disease recurrence or death relative to placebo at both 2 and 5 years post-randomization in the pivotal ExteNET trial in women with early-stage HER2-positive breast cancer who had completed adjuvant trastuzumab. Subgroup analyses showed that patients with hormone receptor (HRc)-positive disease derived greater benefit with neratinib than patients with HRc-negative disease, and patients who initiated neratinib within 1 year of completing trastuzumab had better outcomes than those who started treatment 1-2 years after trastuzumab. This led to the approval of neratinib in the EU as extended adjuvant therapy for patients with early-stage HRc-positive, HER2-positive breast cancer and who are less than 1 year from completion of prior adjuvant trastuzumab-based therapy. It is the first agent of its class to be approved in the EU in this setting. As with other tyrosine kinase inhibitors, diarrhoea, which was manageable with antidiarrhoeal prophylaxis and/or dose modifications, was the most common any-grade or grade ≥ 3 treatment-emergent adverse event with neratinib. Thus, current evidence indicates that neratinib provides a valuable option to reduce the risk of recurrence in this setting and has been included in the updated ESMO patient guide as an extended adjuvant therapy for some patients.