Treating disease progression with osimertinib in EGFR-mutated non-small-cell lung cancer: novel targeted agents and combination strategies.

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Abstrakt

Tytuł:: Treating disease progression with osimertinib in EGFR-mutated non-small-cell lung cancer: novel targeted agents and combination strategies.
Autorzy:: Di Noia V; Medical Oncology 1 Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy. Electronic address: .
D'Aveni A; Department of Medical Oncology 1, Cliniche Humanitas Gavazzeni, Bergamo, Italy.
D'Argento E; Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Rossi S; Department of Oncology and Hematology, Humanitas Clinical and Research Center, Rozzano, Italy.
Ghirardelli P; Department of Medical Oncology 1, Cliniche Humanitas Gavazzeni, Bergamo, Italy.
Bortolotti L; Department of Medical Oncology 1, Cliniche Humanitas Gavazzeni, Bergamo, Italy.
Vavassori V; Department of Medical Oncology 1, Cliniche Humanitas Gavazzeni, Bergamo, Italy.
Bria E; Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Istituto di Medicina Interna e Geriatria, Università; Cattolica del Sacro Cuore, Rome, Italy.
Ceresoli GL; Department of Medical Oncology 1, Cliniche Humanitas Gavazzeni, Bergamo, Italy.
Źródło:: ESMO open [ESMO Open] 2021 Dec; Vol. 6 (6), pp. 100280. Date of Electronic Publication: 2021 Oct 09.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't; Review
Język:: English
Imprint Name(s):: Publication: 2021 : [London] : Elsevier
Original Publication: London : BMJ, [2016]-
MeSH Terms:: Carcinoma, Non-Small-Cell Lung*/drug therapy
Carcinoma, Non-Small-Cell Lung*/genetics
Lung Neoplasms*/drug therapy
Lung Neoplasms*/genetics
Acrylamides ; Aniline Compounds ; Disease Progression ; ErbB Receptors/genetics ; Humans ; Mutation ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use
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Contributed Indexing:: Keywords: EGFR; non-small-cell lung cancer; osimertinib; progression; tyrosine kinase inhibitors
Substance Nomenclature:: 0 (Acrylamides)
0 (Aniline Compounds)
0 (Protein Kinase Inhibitors)
3C06JJ0Z2O (osimertinib)
EC 2.7.10.1 (EGFR protein, human)
EC 2.7.10.1 (ErbB Receptors)
Entry Date(s):: Date Created: 20211011 Date Completed: 20220324 Latest Revision: 20231107
Update Code:: 20240104
PubMed Central ID:: PMC8506968
DOI:: 10.1016/j.esmoop.2021.100280
PMID:: 34634633
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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.
Competing Interests: 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.
(Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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