Candidate mechanisms of acquired resistance to first-line osimertinib in EGFR-mutated advanced non-small cell lung cancer.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 02 2023
27 02 2023
Historique:
received:
28
07
2021
accepted:
10
01
2023
entrez:
27
2
2023
pubmed:
28
2
2023
medline:
3
3
2023
Statut:
epublish
Résumé
Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), potently and selectively inhibits EGFR-TKI-sensitizing and EGFR T790M resistance mutations. In the Phase III FLAURA study (NCT02296125), first-line osimertinib improved outcomes vs comparator EGFR-TKIs in EGFRm advanced non-small cell lung cancer. This analysis identifies acquired resistance mechanisms to first-line osimertinib. Next-generation sequencing assesses circulating-tumor DNA from paired plasma samples (baseline and disease progression/treatment discontinuation) in patients with baseline EGFRm. No EGFR T790M-mediated acquired resistance are observed; most frequent resistance mechanisms are MET amplification (n = 17; 16%) and EGFR C797S mutations (n = 7; 6%). Future research investigating non-genetic acquired resistance mechanisms is warranted.
Identifiants
pubmed: 36849494
doi: 10.1038/s41467-023-35961-y
pii: 10.1038/s41467-023-35961-y
pmc: PMC9971254
doi:
Substances chimiques
osimertinib
3C06JJ0Z2O
ErbB Receptors
EC 2.7.10.1
Protein Kinase Inhibitors
0
EGFR protein, human
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1070Subventions
Organisme : NCI NIH HHS
ID : P30 CA138292
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. The Author(s).
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