Treating disease progression with osimertinib in EGFR-mutated non-small-cell lung cancer: novel targeted agents and combination strategies.
EGFR
non-small-cell lung cancer
osimertinib
progression
tyrosine kinase inhibitors
Journal
ESMO open
ISSN: 2059-7029
Titre abrégé: ESMO Open
Pays: England
ID NLM: 101690685
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
12
05
2021
revised:
09
09
2021
accepted:
10
09
2021
pubmed:
12
10
2021
medline:
25
3
2022
entrez:
11
10
2021
Statut:
ppublish
Résumé
A precision medicine approach has been successfully applied in medical oncology for the treatment of non-small-cell lung cancer (NSCLC) through the identification of targetable driver molecular aberrations; activating mutations of epidermal growth factor receptor (EGFR) are the most common. Osimertinib, a third-generation, wild-type sparing, irreversible EGFR tyrosine kinase inhibitor (TKI), originally showed a striking activity after progression to first- and second-generation EGFR-TKIs when T790M resistance mutation was identified. Thereafter, upfront use of osimertinib became the standard of care based on overall survival benefit over first-generation TKIs erlotinib and gefitinib as reported in the FLAURA trial. For patients progressing on osimertinib, identification of resistance mechanisms is crucial to develop novel targeted therapeutic approaches. Moreover, innovative drugs or combination therapies are being developed for cases in which a specific resistance mechanism is not identifiable. In this review, the post-osimertinib treatment options for EGFR-mutated NSCLC are analyzed, with an outlook to ongoing clinical trials. An algorithm to guide clinicians in managing progression on osimertinib is proposed.
Identifiants
pubmed: 34634633
pii: S2059-7029(21)00242-8
doi: 10.1016/j.esmoop.2021.100280
pmc: PMC8506968
pii:
doi:
Substances chimiques
Acrylamides
0
Aniline Compounds
0
Protein Kinase Inhibitors
0
osimertinib
3C06JJ0Z2O
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
100280Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Disclosure VDN received speakers’ fees from AstraZeneca, MSD, BMS, Istituto Gentili, and Boehringer Ingelheim; grant consultancies from AstraZeneca, MSD, BMS, and Boehringer Ingelheim; travel fees from MSD and Boehringer Ingelheim; and institutional research grants from Roche. EB received speakers’ and travel fees from MSD, AstraZeneca, Celgene, Pfizer, Helsinn, Eli-Lilly, BMS, Novartis, and Roche; consultant fees from Roche and Pfizer; and received institutional research grants from AstraZeneca and Roche. GLC received speakers’ fees from Novocure, Zai Lab, and MSD and consultant fees from Novocure and Zai Lab. The remaining authors have declared no conflicts of interest.
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