Lingyun Ye1, Xiaoxia Chen, Fei Zhou. 1. Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
Abstract
PURPOSE OF REVIEW: Despite the significant advances in EGFR-mutant nonsmall cell lung cancer (NSCLC), some challenges remain. One of the permanent and inevitable issues is the emergence of acquired resistance. Therefore, blocking the activation of EGFR pathway and overcoming drug resistance with novel agents are still in high demand. Here, we review the development of novel drugs in EGFR-mutant, advanced NSCLC, including targeting EGFR exon 20 insertion (EGFR20ins), and novel role of epidermal growth factor receptor, tyrosine kinase inhibitor (EGFR-TKIs) in early-stage NSCLC. RECENT FINDINGS: EGFR-TKIs as adjuvant therapy or neoadjuvant therapy in patients with early-stage NSCLC with EGFR-sensitizing mutations have shown promising efficacy. The resistance mechanisms of third-generation EGFR-TKIs can be divided into two types: EGFR dependent and EGFR independent. Several clinical trials have demonstrated that the addition of MET inhibitors to EGFR-TKIs was an effective option for patients who had acquired resistance to EGFR-TKIs caused by hepatocyte growth factor receptor gene (MET) amplification or overexpression. Novel compounds that selectively and potently inhibit EGFR20ins are being investigated in phase III studies. SUMMARY: A better characterization and understanding of resistance mechanisms to first-line osimertinib and adjuvant osimertinib is helpful to guide further treatment.
PURPOSE OF REVIEW: Despite the significant advances in EGFR-mutant nonsmall cell lung cancer (NSCLC), some challenges remain. One of the permanent and inevitable issues is the emergence of acquired resistance. Therefore, blocking the activation of EGFR pathway and overcoming drug resistance with novel agents are still in high demand. Here, we review the development of novel drugs in EGFR-mutant, advanced NSCLC, including targeting EGFR exon 20 insertion (EGFR20ins), and novel role of epidermal growth factor receptor, tyrosine kinase inhibitor (EGFR-TKIs) in early-stage NSCLC. RECENT FINDINGS:EGFR-TKIs as adjuvant therapy or neoadjuvant therapy in patients with early-stage NSCLC with EGFR-sensitizing mutations have shown promising efficacy. The resistance mechanisms of third-generation EGFR-TKIs can be divided into two types: EGFR dependent and EGFR independent. Several clinical trials have demonstrated that the addition of MET inhibitors to EGFR-TKIs was an effective option for patients who had acquired resistance to EGFR-TKIs caused by hepatocyte growth factor receptor gene (MET) amplification or overexpression. Novel compounds that selectively and potently inhibit EGFR20ins are being investigated in phase III studies. SUMMARY: A better characterization and understanding of resistance mechanisms to first-line osimertinib and adjuvant osimertinib is helpful to guide further treatment.