Neratinib

Neratinib is a small-molecule oral tyrosine kinase inhibitor that irreversibly inhibits members of the ErbB/HER receptor family, most notably human epidermal growth factor receptor 2 (HER2), as well as EGFR (HER1) and HER4. By covalently binding to the ATP-binding pocket, it prevents receptor phosphorylation and downstream signaling that promote tumor cell growth. As a pan-HER inhibitor, neratinib is used primarily in HER2-positive cancers and has activity in tumors with HER2 amplification.

In the United States, neratinib is approved for two main indications in breast cancer: extended adjuvant therapy for early-stage, HER2-positive breast cancer following completion of trastuzumab-based therapy (given for about one year); and treatment of metastatic HER2-positive breast cancer in adults in combination with capecitabine after prior therapy for metastatic disease.

Neratinib is taken orally once daily with food, at a dose of 240 mg, with the adjuvant use lasting one year. When used for metastatic disease, it is given in combination with capecitabine according to the labeled dosing schedule.

The most common adverse event is diarrhea, which can be severe; prophylactic antidiarrheal therapy is often recommended, especially during the initial cycles. Other frequent side effects include nausea, vomiting, fatigue, rash, and abdominal pain. Rare but serious risks include hepatotoxicity and pneumonitis. Patients are monitored for diarrhea, liver function, hydration, and electrolyte balance.