Neratinib: an oral, irreversible dual EGFR/HER2 inhibitor for breast and non-small cell lung cancer

Expert Opin Investig Drugs. 2009 Nov;18(11):1735-51. doi: 10.1517/13543780903305428.


Background: The revolutionary success of imatinib, a specific inhibitor of the BCR-ABL tyrosine kinase (TK) in the treatment of chronic myelogenous leukemia ushered in the era of targeted therapies in cancer. The erythroblastic leukemia viral oncogene homolog family of receptor TKs, to which EGFR (HER1) and human epidermal growth factor receptor 2 (HER2)/neu TKs belong, has been implicated in a variety of cancers, and several agents that inhibit these TKs are in clinical use, with many more in various stages of development.

Objectives: To summarize current knowledge about neratinib (HKI-272), an oral, irreversible dual inhibitor of EGFR and HER2 and to define its future clinical role, especially in the context of related agents that are either available or in the pipeline.

Methods: A Medline search using Pubmed was conducted using the keywords neratinib, HKI-272, EGFR, HER2, lapatinib, trastuzumab, erlotinib, gefitinib, cetuximab and panitumumab. Relevant abstracts presented at the American Society of Clinical Oncology and San Antonio Breast Cancer Symposium meetings were also reviewed.

Conclusions: Both preclinical and human studies have shown that neratinib has promising activity in both advanced breast cancer and NSCLC with an acceptable safety profile. The data support its continued clinical development.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / physiopathology
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / physiopathology
  • ErbB Receptors / antagonists & inhibitors
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / physiopathology
  • Quinolines / adverse effects
  • Quinolines / pharmacology
  • Quinolines / therapeutic use*
  • Receptor, ErbB-2 / antagonists & inhibitors


  • Antineoplastic Agents
  • Quinolines
  • ERBB2 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • neratinib