Analysis of acquired resistance mechanisms to osimertinib in patients with EGFR-mutated advanced non-small cell lung cancer from the AURA3 trial.
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. This analysis evaluates acquired resistance mechanisms to second-line osimertinib (n = 78) in patients with EGFR T790M advanced non-small cell lung cancer (NSCLC) from AURA3 (NCT02151981), a randomized phase 3 study comparing osimertinib with chemotherapy. Plasma samples collected at baseline and disease progression/treatment discontinuation are analyzed using next-generation sequencing. Half (50%) of patients have undetectable plasma EGFR T790M at disease progression and/or treatment discontinuation. Fifteen patients (19%) have >1 resistance-related genomic alteration; MET amplification (14/78, 18%) and EGFR C797X mutation (14/78, 18%).
Identifiants
pubmed: 36849516
doi: 10.1038/s41467-023-35962-x
pii: 10.1038/s41467-023-35962-x
pmc: PMC9971022
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
1071Subventions
Organisme : NCI NIH HHS
ID : P30 CA138292
Pays : United States
Informations de copyright
© 2023. The Author(s).
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