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Cited 81 time in webofscience Cited 87 time in scopus
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Recent Advances on the Role of EGFR Tyrosine Kinase Inhibitors in the Management of NSCLC With Uncommon, Non Exon 20 Insertions, EGFR Mutations

Authors
Passaro, A.[Passaro, A.]Mok, T.[Mok, T.]Peters, S.[Peters, S.]Popat, S.[Popat, S.]Ahn, M.-J.[Ahn, M.-J.]de, Marinis F.[de, Marinis F.]
Issue Date
May-2021
Publisher
Elsevier Inc.
Keywords
Afatinib; Dacomitinib; EGFR; Lung cancer; Osimertinib; Uncommon mutation
Citation
Journal of Thoracic Oncology, v.16, no.5, pp.764 - 773
Indexed
SCIE
SCOPUS
Journal Title
Journal of Thoracic Oncology
Volume
16
Number
5
Start Page
764
End Page
773
URI
https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/1869
DOI
10.1016/j.jtho.2020.12.002
ISSN
1556-0864
Abstract
The first-line treatment of choice for patients with EGFR mutation-positive NSCLC is an EGFR tyrosine kinase inhibitor (TKI), of which five as follows are predominantly available in practice: gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib. Most prospective clinical trial data with these agents are limited to patients with the common activating and sensitizing EGFR mutations as follows: exon 19 deletions and exon 21 L858R point mutations. However, 10% to 20% of patients with NSCLC harbor uncommon EGFR mutations that have variable sensitivity to different EGFR TKIs. Owing to their molecular structures, afatinib, dacomitinib, and osimertinib have broader inhibitory profiles than the first-generation agents, gefitinib and erlotinib. Nevertheless, the paucity of prospective clinical data, the wide heterogeneity of uncommon mutations, and the existence of compound mutations in up to 25% of the cases complicate treatment decisions in this patient subgroup. Here, we collate the latest preclinical and clinical data regarding the activity of different TKIs against major uncommon EGFR mutations including compound mutations, but excluding exon 20 insertions which are generally insensitive to TKIs. On the basis of these data, we offer suggestions regarding treatment strategies for uncommon EGFR mutations. Moving forward, it will be important to include uncommon EGFR mutations in the first-line molecular analysis of all patients with adenocarcinoma of the lung, as this will help optimize patient outcomes according to their precise genotype. © 2020 International Association for the Study of Lung Cancer
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