EGFR exon 20 insertions in advanced non-small cell lung cancer: A new history begins

Autores organización

• 

  Andres Felipe Cardona Mendoza

  Autor

Autores

• Remon J
• Hendriks LEL
• Besse B

Grupos de investigación

• Grupo de Inmunología celular y molecular Universidad El Bosque (InmuBo)

  Investigador

  Maria Consuelo Romero Sanchez

Resumen

Although targeted therapy is standard of care in a large subset of oncogenic addicted non-small cell lung cancers (NSCLC), until recently, this therapeutic approach has not been feasible for all genomic alterations such as for those tumors harboring Epidermal Growth Factor Receptor (EGFR) exon 20 insertion (ex20ins) mutations. Despite being the third most common EGFR mutation, a limited efficacy of first- and second-generation EGFR tyrosine kinase inhibitors (TKI) exists. This is related to the heterogeneity at the molecular level in EGFR ex20ins mutation variants and the finding that this mutation promotes active kinase conformation but does not increase the affinity for EGFR TKI. As a result, the prognosis of this population is diminished. Therefore, chemotherapy remained the most suitable strategy in this subset of EGFR mutant NSCLC patients. Recently, new treatment strategies have been reported in this landscape, either with new EGFR TKI or bispecific antibodies, which may establish a new standard of care in the coming future for these patients. Future research should focus on elucidating the oncogenic degree of all EGFR ex20ins variants, the potential role of combination strategies either with chemotherapy or immune checkpoint inhibitors, and the most appropriate first-line treatment strategy in this subgroup. Finally, the knowledge of mechanisms of acquired resistance to these new agents upon progression is a priority for personalising treatment at that time. It is in this framework, that we provide a thorough overview on this subject. © 2020 Elsevier Ltd

Copyright © 2020 Elsevier Ltd. All rights reserved.

Keywords

• Animals; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; ErbB Receptors; Exons; Genes, erbB-1; Humans; Lung Neoplasms; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic; amivantamab; bispecific antibody; epidermal growth factor receptor; epidermal growth factor receptor kinase inhibitor; immune checkpoint inhibitor; immunological antineoplastic agent; jnj 61186372; mobocertinib; osimertinib; poziotinib; tarloxotinib; tas 6417; unclassified drug; antineoplastic agent; epidermal growth factor receptor; protein kinase inhibitor; advanced cancer; cancer chemotherapy; cancer immunotherapy; cancer prognosis; cancer resistance; cancer survival; chemosensitivity; diarrhea; drug efficacy; drug safety; drug tolerability; EGFR gene; enzyme conformation; exon; gene insertion; gene mutation; genetic heterogeneity; genetic variability; human; molecular genetics; non small cell lung cancer; outcome assessment