Are there any serious side effects of neratinib/neratinib?

Neratinib/Neratinib is an oral, irreversible pan-HER tyrosine kinase inhibitor that was approved by the U.S. Food and Drug Administration (FDA) in 2017 and authorized by the European Commission in 2018 as an extended adjuvant treatment for patients with HER2-positive breast cancer. In cancer, neratinib shows its efficacy by irreversibly inhibiting the epidermal growth factor receptor (EGFR) family, which includes EGFR (HER1), HER2, and HER4. Like many other tyrosine kinase inhibitors, neratinib has devastating toxicities, particularly a high incidence of gastrointestinal (GI) side effects.

In the Phase III study of neratinib (ExteNET), the most common adverse event was diarrhea. Up to 96% of cancer patients taking neratinib experienced various degrees of diarrhea, with 40% experiencing grade 3-4 diarrhea. This adverse event resulted in 17% of patients discontinuing treatment. Severe diarrhea may lead to dehydration and kidney failure, ultimately hindering the therapeutic effect of neratinib. In the clinical setting, complete neratinib treatment lasts for 1 year, with diarrhea occurring mainly during the first month of the treatment cycle. Therefore, patients taking neratinib should be provided with drugs or nutrients that benefit intestinal homeostasis, regardless of whether they have diarrhea or not.

Antidiarrheal prophylaxis has been shown to reduce the incidence and severity of diarrhea. During the patient's medication, the doctor will instruct the patient to use loperamide for antidiarrheal prevention while taking the first dose of neratinib, and continue to use it for the first 56 days of treatment; after the 56th day, the dose will be titrated to achieve 1-2 bowel movements per day, and no more than 16 mg of loperamide per day. Consider adding other drugs to loperamide as clinically indicated.