Candidate mechanisms of acquired resistance to first-line osimertinib in EGFR-mutated advanced non-small cell lung cancer

Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), potently and selectively inhibits EGFR-TKI-sensitizing and EGFR T790M resistance mutations. In the Phase III FLAURA study (NCT02296125), first-line osimertinib improved outcomes vs comparator EGFR-TKIs in EGFRm ad...

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Autores principales: Chmielecki, Juliann, Gray, Jhanelle E., Cheng, Ying, Ohe, Yuichiro, Imamura, Fumio, Cho, Byoung Chul, Lin, Meng-Chih, Majem, Margarita, Shah, Riyaz, Rukazenkov, Yuri, Todd, Alexander, Markovets, Aleksandra, Barrett, J. Carl, Hartmaier, Ryan J., Ramalingam, Suresh S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9971254/
https://www.ncbi.nlm.nih.gov/pubmed/36849494
http://dx.doi.org/10.1038/s41467-023-35961-y
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author Chmielecki, Juliann
Gray, Jhanelle E.
Cheng, Ying
Ohe, Yuichiro
Imamura, Fumio
Cho, Byoung Chul
Lin, Meng-Chih
Majem, Margarita
Shah, Riyaz
Rukazenkov, Yuri
Todd, Alexander
Markovets, Aleksandra
Barrett, J. Carl
Hartmaier, Ryan J.
Ramalingam, Suresh S.
author_facet Chmielecki, Juliann
Gray, Jhanelle E.
Cheng, Ying
Ohe, Yuichiro
Imamura, Fumio
Cho, Byoung Chul
Lin, Meng-Chih
Majem, Margarita
Shah, Riyaz
Rukazenkov, Yuri
Todd, Alexander
Markovets, Aleksandra
Barrett, J. Carl
Hartmaier, Ryan J.
Ramalingam, Suresh S.
author_sort Chmielecki, Juliann
collection PubMed
description Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), potently and selectively inhibits EGFR-TKI-sensitizing and EGFR T790M resistance mutations. In the Phase III FLAURA study (NCT02296125), first-line osimertinib improved outcomes vs comparator EGFR-TKIs in EGFRm advanced non-small cell lung cancer. This analysis identifies acquired resistance mechanisms to first-line osimertinib. Next-generation sequencing assesses circulating-tumor DNA from paired plasma samples (baseline and disease progression/treatment discontinuation) in patients with baseline EGFRm. No EGFR T790M-mediated acquired resistance are observed; most frequent resistance mechanisms are MET amplification (n = 17; 16%) and EGFR C797S mutations (n = 7; 6%). Future research investigating non-genetic acquired resistance mechanisms is warranted.
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spelling pubmed-99712542023-03-01 Candidate mechanisms of acquired resistance to first-line osimertinib in EGFR-mutated advanced non-small cell lung cancer Chmielecki, Juliann Gray, Jhanelle E. Cheng, Ying Ohe, Yuichiro Imamura, Fumio Cho, Byoung Chul Lin, Meng-Chih Majem, Margarita Shah, Riyaz Rukazenkov, Yuri Todd, Alexander Markovets, Aleksandra Barrett, J. Carl Hartmaier, Ryan J. Ramalingam, Suresh S. Nat Commun Article Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), potently and selectively inhibits EGFR-TKI-sensitizing and EGFR T790M resistance mutations. In the Phase III FLAURA study (NCT02296125), first-line osimertinib improved outcomes vs comparator EGFR-TKIs in EGFRm advanced non-small cell lung cancer. This analysis identifies acquired resistance mechanisms to first-line osimertinib. Next-generation sequencing assesses circulating-tumor DNA from paired plasma samples (baseline and disease progression/treatment discontinuation) in patients with baseline EGFRm. No EGFR T790M-mediated acquired resistance are observed; most frequent resistance mechanisms are MET amplification (n = 17; 16%) and EGFR C797S mutations (n = 7; 6%). Future research investigating non-genetic acquired resistance mechanisms is warranted. Nature Publishing Group UK 2023-02-27 /pmc/articles/PMC9971254/ /pubmed/36849494 http://dx.doi.org/10.1038/s41467-023-35961-y Text en © The Author(s) 2023, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Chmielecki, Juliann
Gray, Jhanelle E.
Cheng, Ying
Ohe, Yuichiro
Imamura, Fumio
Cho, Byoung Chul
Lin, Meng-Chih
Majem, Margarita
Shah, Riyaz
Rukazenkov, Yuri
Todd, Alexander
Markovets, Aleksandra
Barrett, J. Carl
Hartmaier, Ryan J.
Ramalingam, Suresh S.
Candidate mechanisms of acquired resistance to first-line osimertinib in EGFR-mutated advanced non-small cell lung cancer
title Candidate mechanisms of acquired resistance to first-line osimertinib in EGFR-mutated advanced non-small cell lung cancer
title_full Candidate mechanisms of acquired resistance to first-line osimertinib in EGFR-mutated advanced non-small cell lung cancer
title_fullStr Candidate mechanisms of acquired resistance to first-line osimertinib in EGFR-mutated advanced non-small cell lung cancer
title_full_unstemmed Candidate mechanisms of acquired resistance to first-line osimertinib in EGFR-mutated advanced non-small cell lung cancer
title_short Candidate mechanisms of acquired resistance to first-line osimertinib in EGFR-mutated advanced non-small cell lung cancer
title_sort candidate mechanisms of acquired resistance to first-line osimertinib in egfr-mutated advanced non-small cell lung cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9971254/
https://www.ncbi.nlm.nih.gov/pubmed/36849494
http://dx.doi.org/10.1038/s41467-023-35961-y
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