title: Afatinib in the treatment of breast cancer.
abstract: BACKGROUND
  Trastuzumab has dramatically improved outcomes for those diagnosed with human EGFR2 (HER2)-positive breast cancer. Resistance to trastuzumab, however, is an ongoing problem that has led to the development of a number of new HER2-targeted therapies. Afatinib is a novel, orally bioavailable irreversible pan-HER inhibitor that has been evaluated in multiple tumor types. It has also shown promise in NSCLC where it has earned FDA approval. Its activity in breast cancer is currently being evaluated.
  
  
  METHODS
  This review briefly summarizes the current therapies available for HER2-positive metastatic disease. This article also describes the data available for afatinib in breast cancer from preclinical analyses, published Phase I and II trials to ongoing and upcoming Phase II and III studies.
  
  
  CONCLUSIONS
  While Phase I and II studies have demonstrated promising activity in HER2-positive breast cancer, the Phase III randomized study of afatinib in trastuzumab-resistant metastatic breast cancer was halted early due to unfavorable risk-benefit analysis from the Independent Data Monitoring Committee (IDMC). The successful development of afatinib in breast cancer will thus depend on aggressively preventing and managing its associated toxicities.
authors.affiliation: University of California, Division of Hematology-Oncology, Department of Medicine , 10945 Le Conte Avenue, PVUB Suite 3360, Los Angeles, CA 90095 , USA +1 310 829 5471 ; +1 310 829 6192 ; shurvitz@mednet.ucla.edu.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Hurvitz
authors.forename: Rebecca
authors.initials: R
authors.lastname: Shatsky
authors.forename: Nadia
authors.initials: N
authors.lastname: Harbeck
mesh_terms: D000077716:Afatinib; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000077716:Afatinib; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases
keywords: afatinib; human epidermal growth factor receptor2; metastatic breast cancer; tyrosine kinase inhibitor