EGFR exon 20 insertions in advanced non-small cell lung cancer: A new history begins |
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| Institution: | 1. Department of Medical Oncology, Centro Integral Oncológico Clara Campal (HM-CIOCC), Hospital HM Delfos, HM Hospitales, Barcelona, Spain;2. Department of Respiratory Medicine, Maastricht University Medical Centre, GROW School for Oncology and Developmental Biology, Maastricht, the Netherlands;3. Clinical and Translational Oncology Group, Clínica del Country, Bogotá, Colombia;4. Foundation for Clinical and Applied Cancer Research – FICMAC, Bogotá, Colombia;5. Clinical Research and Biology Systems Department, Universidad el Bosque, Bogotá, Colombia;6. Gustave Roussy, Department of Cancer Medicine, Villejuif, France;7. Université Paris-Saclay, Orsay, France;1. Clinical and Translational Oncology Group, Clínica del Country, Bogotá, Colombia;2. Foundation for Clinical and Applied Cancer Research – FICMAC, Bogotá, Colombia;3. Clinical Research and Biology Systems Department, Universidad el Bosque, Bogotá, Colombia;4. Internal Medicine Department, Pontificia Universidad Javeriana, Bogotá, Colombia;5. Clinical Oncology Department, Clínica Colsanitas, Bogotá, Colombia;6. Thoracic Oncology Unit, National Cancer Institute (INCan), México City, Mexico;7. A.C. Camargo Cancer Center, São Paulo, Brazil;8. Instituto Oncológico Nacional, Panamá City, Panama;9. Hospital Oncológico Luis Razetti, Caracas, Venezuela;10. Oncology Department, Hospital San Juan de Dios, San José Costa Rica, Costa Rica;11. Medical Oncology Group, Fleming Institute, Buenos Aires, Argentina;12. Arsuve, Caracas, Venezuela;13. Clínica de Prevención del Cáncer, Caracas, Venezuela;14. Oncology Department, Clínica Astorga, Medellín, Colombia;15. Oncology Department, Clínica Porto Azul, Barranquilla, Colombia;p. Translational Research Unit, Coyote Group, IOR/Dexeus University Hospital, Barcelona, Spain;q. Internal Medicine Department, Johns Hopkins University, Baltimore, Maryland, United States;r. Oncology Department, Institute of Oncology, Fundación Santa Fe de Bogotá, Bogotá, Colombia;s. Thoracic Oncology Unit, A.C. Camargo Cancer Center, São Paulo, Brazil;t. Personalized Medicine Program, Catalan Institute of Oncology – ICO, Barcelona, Spain;1. Graduate Institute of Oncology, National Taiwan University and National Taiwan University Hospital, Taiwan;2. Massachusetts General Hospital Cancer Center, Boston, MA, USA;3. Internal Medicine, Faculty of Medicine, Prince of Songkla University, Thailand;4. Department of Chest Medicine, Taipei Veterans General Hospital and School of Medicine National Yang-Ming University, Taipei, Taiwan;5. Clinical Oncology, The Chinese University of Hong Kong, Hong Kong;6. West German Cancer Center, Department of Medical Oncology, University Hospital Essen, Germany and German Cancer Consortium (DKTK), Heidelberg, Germany;7. Third Department of Internal Medicine, Wakayama Medical University, Japan;8. Department of Internal Medicine, National Taiwan University and National Taiwan University Hospital, Taiwan;9. Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, CA, USA;10. Shanghai Pulmonary Hospital, Shanghai, China;11. Clinical Development and Medical Affairs, Bracknell, UK;12. Boehringer Ingelheim, Bracknell, UK;13. Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, China;1. Seoul National University Cancer Research Institute, Seoul, Republic of Korea;2. Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea;3. Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea;1. University of California San Diego School of Medicine, 9500 Gilman Dr, La Jolla, CA, 92093, USA;2. Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, 3855 Health Sciences Dr, La Jolla, CA, 92093, USA;3. Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital, Passeig de la Vall d''Hebron, 119, 129, 08035, Barcelona, Spain |
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| Abstract: | 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. |
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| Keywords: | EGFR exon 20 insertions Poziotinib TAK-788 Amivantamab Osimertinib |
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