afatinib + trastuzumab

Afatinib + trastuzumab is a combination therapy consisting of afatinib, an irreversible oral small-molecule inhibitor of the ErbB family of receptor tyrosine kinases, and trastuzumab, a monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER2/ErbB2). Afatinib blocks signaling from all ErbB family members (EGFR/ErbB1, HER2/ErbB2, ErbB3, and ErbB4) by covalently binding to their kinase domains and irreversibly inhibiting autophosphorylation. Trastuzumab binds to the extracellular domain of HER2 and inhibits its activity. The combination has been investigated primarily in patients with HER2-positive metastatic breast cancer who have developed resistance to trastuzumab monotherapy. Clinical studies indicate that this regimen can show clinical activity in trastuzumab-refractory disease but is associated with significant gastrointestinal toxicity (notably diarrhea), requiring careful management[1][2][6]. Preclinical data also support its use in other HER2-positive cancers such as gastric cancer[3][6].