The advance of the third-generation EGFR-TKI in the treatment of non-small cell lung cancer

Lung cancer is currently the second most common type of cancer with the second incidence rate and the first mortality rate worldwide. Non-small cell lung cancer (NSCLC) accounts for similar to 85% of the total number of cases of lung cancers. Concerning the treatment of NSCLC, targeted therapy has become a research hotspot in recent years because of its favorable efficacy, high selectivity and minimal adverse reactions. Among the drugs used in targeted therapy, the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the most common and are categorized into four generations. The use of first and second-generation drugs leads to drug resistance within 8-14 months. This resistance is primarily caused by the T790M mutation, which is the most observed mechanism. A third-generation drug has been developed to address this issue and a fourth-generation drug is expected to overcome multiple resistance mechanisms, including third-generation drug resistance. However, the fourth-generation drug has not been launched yet. At present, multiple third-generation targeted drugs have been launched globally, with three being launched in China and several being at research and clinical trial stages. The present article provides a review of the development process, mechanism of action and clinical trials of the third-generation EGFR-TKIs, aiming to provide some reference and suggestions for the clinical treatment of NSCLC and scientific research on third-generation targeted drugs.