Neratinib for HER2-positive breast cancer with an overlooked option

Molecular Medicine

Review

Junqing Wang¹  Yan Shi²  Liting Guo³  Jun Zhang³  Chenfei Zhou³  Liu Yang³  Hui Yang³  Qu Cai³  Lei Huang⁴  Weiwei Shao⁵ 

[1] Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, 200025, Shanghai, China;Department of General Surgery, Shanghai Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, 358 Datong Road, Gaoqiao Town, 200137, Shanghai, China;Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, 200025, Shanghai, China;Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, 200025, Shanghai, China;Medical Center on Aging of Ruijin Hospital, MCARJH, Shanghai Jiaotong University School of Medicine, Shanghai, China;Department of Pathology, The First People’s Hospital of Yancheng City, Yancheng, China;

关键词: Neratinib;    Breast cancer;    HER2;    Central nervous system metastasis;   

DOI  :  10.1186/s10020-023-00736-0

 received in 2023-04-16, accepted in 2023-09-28,  发布年份 2023

来源: Springer

【 摘 要 】

Positive human epidermal growth factor receptor 2 (HER2) expression is associated with an increased risk of metastases especially those to the brain in patients with advanced breast cancer (BC). Neratinib as a tyrosine kinase inhibitor can prevent the transduction of HER1, HER2 and HER4 signaling pathways thus playing an anticancer effect. Moreover, neratinib has a certain efficacy to reverse drug resistance in patients with BC with previous HER2 monoclonal antibody or targeted drug resistance. Neratinib, as monotherapy and in combination with other therapies, has been tested in the neoadjuvant, adjuvant, and metastatic settings. Neratinib with high anticancer activity is indicated for the prolonged adjuvant treatment of HER2-positive early BC, or in combination with other drugs including trastuzumab, capecitabine, and paclitaxel for the treatment of advanced HER2-positive BC especially cancers with central nervous system (CNS) metastasis to reduce the risk of BC recurrence. This article reviewed the pharmacological profiles, efficacy, safety, tolerability, and current clinical trials pertaining to neratinib, with a particular focus on the use of neratinib in patients with metastatic breast cancer (MBC) involving the CNS. We further discussed the use of neratinib for HER2-negative and HER2-mutant breast cancers, and mechanisms of resistance to neratinib. The current evidence suggests that neratinib has promising efficacy in patients with BC which is at least non-inferior compared to previous therapeutic regimens. The most common AE was diarrhea, and the incidence, severity and duration of neratinib-related grade 3 diarrhea can be reduced with loperamide. Of note, neratinib has the potential to effectively control and prevent brain metastasis in patients with advanced BC, providing a therapeutic strategy for HER2-positive BC.

【 授权许可】

CC BY   
© The Feinstein Institute for Medical Research 2023