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Current treatment strategies for EGFR-mutated non-small cell lung cancer: from first line to beyond osimertinib resistance
Osimertinib, a third-generation EGFR TKI, is the standard therapy for previously untreated EGFR-mutated non-small cell lung cancer patients following the landmark FLAURA study. However, resistance inevitably hinders patient prognosis, increasing the need for new therapeutic strategies beyond osimert...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10311169/ https://www.ncbi.nlm.nih.gov/pubmed/37279591 http://dx.doi.org/10.1093/jjco/hyad052 |
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author | Araki, Taisuke Kanda, Shintaro Horinouchi, Hidehito Ohe, Yuichiro |
author_facet | Araki, Taisuke Kanda, Shintaro Horinouchi, Hidehito Ohe, Yuichiro |
author_sort | Araki, Taisuke |
collection | PubMed |
description | Osimertinib, a third-generation EGFR TKI, is the standard therapy for previously untreated EGFR-mutated non-small cell lung cancer patients following the landmark FLAURA study. However, resistance inevitably hinders patient prognosis, increasing the need for new therapeutic strategies beyond osimertinib. Frontline osimertinib-based combination strategies (platinum-based chemotherapy and angiogenesis inhibitors) are currently being tested primarily to prevent initial resistance. In the later-line setting after osimertinib, many next-line therapeutic candidates have been actively examined in clinical trials. Notably, several drugs with novel mechanisms of action, such as antibody–drug conjugates and EGFR -MET bispecific antibodies, have shown promising efficacy despite the resistance mechanisms and are close to clinical application. In addition, genotype-based target strategies have been investigated for a better understanding of osimertinib resistance mechanisms based on molecular profiling tests at relapse. The C797S mutation and MET gene alterations are commonly identified following osimertinib resistance, for which targeting strategies are actively tested. This review describes current pharmacotherapeutic strategies for EGFR-mutated non-small cell lung cancer based on the results of clinical trials and the latest published data, broadly grouped into two sections: 1) EGFR TKIs-based combination therapy in the front-line setting and 2) novel therapeutic strategies after osimertinib resistance. |
format | Online Article Text |
id | pubmed-10311169 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-103111692023-07-01 Current treatment strategies for EGFR-mutated non-small cell lung cancer: from first line to beyond osimertinib resistance Araki, Taisuke Kanda, Shintaro Horinouchi, Hidehito Ohe, Yuichiro Jpn J Clin Oncol Review Article (Invited) Osimertinib, a third-generation EGFR TKI, is the standard therapy for previously untreated EGFR-mutated non-small cell lung cancer patients following the landmark FLAURA study. However, resistance inevitably hinders patient prognosis, increasing the need for new therapeutic strategies beyond osimertinib. Frontline osimertinib-based combination strategies (platinum-based chemotherapy and angiogenesis inhibitors) are currently being tested primarily to prevent initial resistance. In the later-line setting after osimertinib, many next-line therapeutic candidates have been actively examined in clinical trials. Notably, several drugs with novel mechanisms of action, such as antibody–drug conjugates and EGFR -MET bispecific antibodies, have shown promising efficacy despite the resistance mechanisms and are close to clinical application. In addition, genotype-based target strategies have been investigated for a better understanding of osimertinib resistance mechanisms based on molecular profiling tests at relapse. The C797S mutation and MET gene alterations are commonly identified following osimertinib resistance, for which targeting strategies are actively tested. This review describes current pharmacotherapeutic strategies for EGFR-mutated non-small cell lung cancer based on the results of clinical trials and the latest published data, broadly grouped into two sections: 1) EGFR TKIs-based combination therapy in the front-line setting and 2) novel therapeutic strategies after osimertinib resistance. Oxford University Press 2023-06-03 /pmc/articles/PMC10311169/ /pubmed/37279591 http://dx.doi.org/10.1093/jjco/hyad052 Text en © The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Review Article (Invited) Araki, Taisuke Kanda, Shintaro Horinouchi, Hidehito Ohe, Yuichiro Current treatment strategies for EGFR-mutated non-small cell lung cancer: from first line to beyond osimertinib resistance |
title | Current treatment strategies for EGFR-mutated non-small cell lung cancer: from first line to beyond osimertinib resistance |
title_full | Current treatment strategies for EGFR-mutated non-small cell lung cancer: from first line to beyond osimertinib resistance |
title_fullStr | Current treatment strategies for EGFR-mutated non-small cell lung cancer: from first line to beyond osimertinib resistance |
title_full_unstemmed | Current treatment strategies for EGFR-mutated non-small cell lung cancer: from first line to beyond osimertinib resistance |
title_short | Current treatment strategies for EGFR-mutated non-small cell lung cancer: from first line to beyond osimertinib resistance |
title_sort | current treatment strategies for egfr-mutated non-small cell lung cancer: from first line to beyond osimertinib resistance |
topic | Review Article (Invited) |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10311169/ https://www.ncbi.nlm.nih.gov/pubmed/37279591 http://dx.doi.org/10.1093/jjco/hyad052 |
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