Detailed explanation of the efficacy, role and side effects of neratinib/neratinib

Neratinib/Neratinib is an oral small molecule pan-human TKI that was approved by the U.S. Food and Drug Administration (FDA) in 2017. Neratinib irreversibly binds to epidermal growth factor receptor (EGFR) HER1, HER2 and HER4, can prevent the transduction of HER1, HER2 and HER4 signaling pathways, thereby exerting anti-cancer effects. Moreover, for breast cancer (BC) patients with previous HER2 monoclonal antibody or targeted resistance, neratinib has certain efficacy in reversing resistance.

Neratinib has been tested in the neoadjuvant, adjuvant and metastatic settings as monotherapy and in combination with other therapies. In the I-SPY2 neoadjuvant trial, neratinib combined with trastuzumab improved the pathological complete response (pCR) rate in patients with HER2-positive, hormone receptor (HR)-negative breast cancer. In the ExteNET trial, neratinib has been shown to be effective in extended adjuvant therapy after trastuzumab for HER2-positive early breast cancer.

Current evidence shows that neratinib has favorable efficacy in patients with breast cancer compared with previous treatment options. The most common adverse event was diarrhea, and loperamide reduced the incidence, severity, and duration of neratinib-related grade 3 diarrhea. Notably, neratinib has the potential to effectively control and prevent brain metastases in patients with advanced breast cancer, providing a therapeutic strategy for HER2-positive breast cancer.

Therefore neratinib with high anti-cancer activity is suitable for long-term adjuvant treatment of HER2-positive early breast cancer, or in combination with other drugs such as trastuzumab, capecitabine and paclitaxel for the treatment of advanced HER2-positive breast cancer, especially cancers with central nervous system (CNS) metastasis, to reduce the risk of breast cancer recurrence and has systemic efficacy and intracranial activity.