Therapeutic exploration of uncommon EGFR exon 20 insertion mutations in advanced non-small cell lung cancer: breaking through brambles and thorns

• Published in: Journal of cancer research and clinical oncology Vol. 148; no. 1; pp. 163 - 176
• Main Authors: Bai, Rilan, Chen, Xiao, Song, Wei, Tian, Huimin, Cui, Jiuwei
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 2022; Springer Nature B.V
• Subjects: Antibodies, Monoclonal - therapeutic use; Antineoplastic Agents - therapeutic use; Cancer Research; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cognition; Drug delivery; Drug development; Drug resistance; Drug Resistance, Neoplasm - genetics; Epidermal growth factor receptors; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - genetics; Hematology; Humans; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Internal Medicine; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Medical prognosis; Medicine; Medicine & Public Health; Molecular modelling; Molecular Structure; Monoclonal antibodies; Mutagenesis, Insertional - genetics; Mutation; Non-small cell lung carcinoma; Oncology; Protein Kinase Inhibitors - therapeutic use; Review – Clinical Oncology; Small cell lung carcinoma; Tumors; Immune checkpoint inhibitor; Bispecific antibody; Tyrosine kinase inhibitor; EGFR exon 20 insertion; Lung cancer
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-021-03840-y

Background EGFR exon 20 insertion (EGFR ex20ins) mutations account for about 10–12% of all EGFR-mutated tumors, which are usually associated with primary drug resistance to conventional EGFR-TKI therapy and worse survival outcomes, and are currently a major problem for clinicians in clinical management. In recent years, with the rapid improvement of sequencing technology and careful review of clinical data, investigators have gained a deeper understanding and clearer cognition of the clinicopathological features and molecular mechanisms of these EGFR ex20ins mutations. Purpose The aim of this study was to systemically review the molecular structure and clinical characteristics of EGFR ex20ins mutations, and focus on summarizing the latest data of emerging therapies (including novel small-molecule EGFR-TKI drugs, specific monoclonal antibodies, novel drugs targeting other mechanisms, and immunotherapy) for those patients. Conclusion Advances in overcoming these systemic challenges have greatly accelerated the development of new drugs targeting EGFR ex20ins, and are committed to designing more rational combination therapies to overcome or delay the emergence of drug resistance, ultimately improve the prognosis of such uncommon mutant populations.