A narrative review of advances in treatment and survival prognosis of HER2-positive malignant lung cancers

Abstract

Human epidermal growth factor receptor 2 (HER2), as a receptor tyrosine kinase of EGF receptor family, whose mutation is often associated with even if less frequency but poor prognosis and shorter survival in pulmonary malignant tumor. HER2 status include mutation, overexpression, amplification and also some rare genotypes, detected by next generation sequencing (NGS), immunohistochemistry (IHC), and also fluorescence in situ hybridization (FISH). Different genotypes represent different therapeutic targets and indicate different clinical prognosis concluded by previous studies. Unfortunately, no standard guidelines for first-line treatment are widely recognized, and current therapeutic schedules include chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Especially for patients with advanced metastasis, chemotherapy is based as a systemic therapy using studies of breast cancer or EGFR-positive lung adenocarcinoma as a template. Studies already explored treatment including EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and afatinib, and also trastuzumab and its conjugation like HER2-targeted antibody-drug conjugate trastuzumab emtansine (T-DM1) and conjugate trastuzumab deruxtecan (T-DXd). Also, he researches explored combination therapy with chemotherapy and TKIs or monoclonal antibodies. This review describes commonly used therapies for HER2-positive/HER2-overexpression patients and general relationship between genotypes of HER2, drug selection and final prognosis in order to provide suggestions for future diagnosis and treatment.