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Review
. 2023 Jan 19;15(3):629.
doi: 10.3390/cancers15030629.

Treatment Strategies for Non-Small Cell Lung Cancer with Common EGFR Mutations: A Review of the History of EGFR TKIs Approval and Emerging Data

Julian A Marin-Acevedo  1 , Bruna Pellini  2   3 , ErinMarie O Kimbrough  4 , J Kevin Hicks  5 , Alberto Chiappori  2   3
Affiliations
Review

Treatment Strategies for Non-Small Cell Lung Cancer with Common EGFR Mutations: A Review of the History of EGFR TKIs Approval and Emerging Data

Julian A Marin-Acevedo et al. Cancers (Basel). .

Abstract

The development of targeted therapies over the past two decades has led to a dramatic change in the management of EGFR-mutant non-small cell lung cancer (NSCLC). While there are currently five approved EGFR tyrosine kinase inhibitors (TKIs) for treating EGFR-mutant NSCLC in the first-line setting, therapy selection after progression on EGFR TKIs remains complex. Multiple groups are investigating novel therapies and drug combinations to determine the optimal therapy and treatment sequence for these patients. In this review, we summarize the landmark trials and history of the approval of EGFR TKIs, their efficacy and tolerability, and the role of these therapies in patients with central nervous system metastasis. We also briefly discuss the mechanisms of resistance to EGFR TKIs, ongoing attempts to overcome resistance and improve outcomes, and finalize by offering treatment sequencing recommendations.

Keywords: EGFR TKIs; EGFR mutations; non-small cell lung cancer; targeted therapies; therapy sequencing.

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Conflict of interest statement

Pellini receives research support from Bristol Myers Squibb (to the institution), has received speaker honoraria from BioAscend, Merck, MJH Life Science, Play to Know AG, Grupo Pardini, Foundation Medicine, and has done consulting/advisory board work with Guidepoint, Guardant Health, Illumina, Regeneron, and AstraZeneca. B.P. reports funding from the Bristol Myers Squibb Foundation/the Robert A. Winn Diversity in Clinical Trials Awards Program, outside of the submitted work. Chiappori receives Research support from Bristol Myers Squibb, AstraZeneca, and Novartis. He has received speaker, consultant and/or advisor honoraria from Blueprint, Takeda, Genentech, Pfizer, Merck, Astra Zeneca, Janssen and Jazz. Hicks received research support from OneOme. Marin-Acevedo and Kimbrough disclose no conflicts.

Figures

Figure 1
Figure 1
Timeline depicting the publication of landmark trials on anti-EGFR TKIs, approval by the FDA and EMA, and publication of data pertaining novel therapies; EMA, European Medicines Agency; FDA, Food and Drugs Administration; TKIs, tyrosine kinase inhibitors. Created with BioRender.com, accessed on 8 January 2023.
See this image and copyright information in PMC

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