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Predictive significance of circulating tumor DNA against patients with T790M-positive EGFR-mutant NSCLC receiving osimertinib

Circulating tumor DNA (ctDNA) provides molecular information on tumor heterogeneity. The prognostic usefulness of ctDNA after first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are limited. Therefore, the present study evaluated ctDNA during osimertinib administrati...

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Autores principales: Yamaguchi, Ou, Kasahara, Norimitsu, Soda, Hiroshi, Imai, Hisao, Naruse, Ichiro, Yamaguchi, Hiroyuki, Itai, Miki, Taguchi, Kohei, Uchida, Megumi, Sunaga, Noriaki, Maeno, Toshitaka, Minato, Koichi, Tomono, Hiromi, Ogawara, Daiki, Mukae, Hiroshi, Miura, Yu, Shiono, Ayako, Mouri, Atsuto, Kagamu, Hiroshi, Kaira, Kyoichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10682450/
https://www.ncbi.nlm.nih.gov/pubmed/38012343
http://dx.doi.org/10.1038/s41598-023-48210-5
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author Yamaguchi, Ou
Kasahara, Norimitsu
Soda, Hiroshi
Imai, Hisao
Naruse, Ichiro
Yamaguchi, Hiroyuki
Itai, Miki
Taguchi, Kohei
Uchida, Megumi
Sunaga, Noriaki
Maeno, Toshitaka
Minato, Koichi
Tomono, Hiromi
Ogawara, Daiki
Mukae, Hiroshi
Miura, Yu
Shiono, Ayako
Mouri, Atsuto
Kagamu, Hiroshi
Kaira, Kyoichi
author_facet Yamaguchi, Ou
Kasahara, Norimitsu
Soda, Hiroshi
Imai, Hisao
Naruse, Ichiro
Yamaguchi, Hiroyuki
Itai, Miki
Taguchi, Kohei
Uchida, Megumi
Sunaga, Noriaki
Maeno, Toshitaka
Minato, Koichi
Tomono, Hiromi
Ogawara, Daiki
Mukae, Hiroshi
Miura, Yu
Shiono, Ayako
Mouri, Atsuto
Kagamu, Hiroshi
Kaira, Kyoichi
author_sort Yamaguchi, Ou
collection PubMed
description Circulating tumor DNA (ctDNA) provides molecular information on tumor heterogeneity. The prognostic usefulness of ctDNA after first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are limited. Therefore, the present study evaluated ctDNA during osimertinib administration as a second-line or more setting to identify the relationship between EGFR mutation levels and outcomes in patients with advanced non-small cell lung cancer (NSCLC). Forty patients with EGFR T790M-positive NSCLC receiving osimertinib after prior EGFR-TKI treatment were registered. Plasma samples were collected at osimertinib pretreatment, after 1 month of treatment, and at the time of progressive disease (PD). ctDNA analysis was performed by digital polymerase chain reaction. The detection rate of copy numbers of exon 19 deletion, L858R, and T790M in plasma samples was significantly lower 1 month after osimertinib than at pretreatment, and significantly higher at PD than at 1 month, whereas that of C797S was significantly higher at PD than at 1 month. No statistically significant difference was observed in the copy numbers of exon 19 deletion, L858R, T790M, and C797S between complete response or partial response and stable disease or PD. The detection of T790M at PD after osimertinib initiation was a significant independent prognostic factor for predicting shorter prognosis, and the presence of major EGFR mutations at pretreatment and PD was closely linked to worse survival after osimertinib initiation. Molecular testing based on ctDNA is helpful for predicting outcomes of osimertinib treatment in T790M-positive NSCLC after previous EGFR-TKI treatment.
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spelling pubmed-106824502023-11-30 Predictive significance of circulating tumor DNA against patients with T790M-positive EGFR-mutant NSCLC receiving osimertinib Yamaguchi, Ou Kasahara, Norimitsu Soda, Hiroshi Imai, Hisao Naruse, Ichiro Yamaguchi, Hiroyuki Itai, Miki Taguchi, Kohei Uchida, Megumi Sunaga, Noriaki Maeno, Toshitaka Minato, Koichi Tomono, Hiromi Ogawara, Daiki Mukae, Hiroshi Miura, Yu Shiono, Ayako Mouri, Atsuto Kagamu, Hiroshi Kaira, Kyoichi Sci Rep Article Circulating tumor DNA (ctDNA) provides molecular information on tumor heterogeneity. The prognostic usefulness of ctDNA after first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are limited. Therefore, the present study evaluated ctDNA during osimertinib administration as a second-line or more setting to identify the relationship between EGFR mutation levels and outcomes in patients with advanced non-small cell lung cancer (NSCLC). Forty patients with EGFR T790M-positive NSCLC receiving osimertinib after prior EGFR-TKI treatment were registered. Plasma samples were collected at osimertinib pretreatment, after 1 month of treatment, and at the time of progressive disease (PD). ctDNA analysis was performed by digital polymerase chain reaction. The detection rate of copy numbers of exon 19 deletion, L858R, and T790M in plasma samples was significantly lower 1 month after osimertinib than at pretreatment, and significantly higher at PD than at 1 month, whereas that of C797S was significantly higher at PD than at 1 month. No statistically significant difference was observed in the copy numbers of exon 19 deletion, L858R, T790M, and C797S between complete response or partial response and stable disease or PD. The detection of T790M at PD after osimertinib initiation was a significant independent prognostic factor for predicting shorter prognosis, and the presence of major EGFR mutations at pretreatment and PD was closely linked to worse survival after osimertinib initiation. Molecular testing based on ctDNA is helpful for predicting outcomes of osimertinib treatment in T790M-positive NSCLC after previous EGFR-TKI treatment. Nature Publishing Group UK 2023-11-27 /pmc/articles/PMC10682450/ /pubmed/38012343 http://dx.doi.org/10.1038/s41598-023-48210-5 Text en © The Author(s) 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Yamaguchi, Ou
Kasahara, Norimitsu
Soda, Hiroshi
Imai, Hisao
Naruse, Ichiro
Yamaguchi, Hiroyuki
Itai, Miki
Taguchi, Kohei
Uchida, Megumi
Sunaga, Noriaki
Maeno, Toshitaka
Minato, Koichi
Tomono, Hiromi
Ogawara, Daiki
Mukae, Hiroshi
Miura, Yu
Shiono, Ayako
Mouri, Atsuto
Kagamu, Hiroshi
Kaira, Kyoichi
Predictive significance of circulating tumor DNA against patients with T790M-positive EGFR-mutant NSCLC receiving osimertinib
title Predictive significance of circulating tumor DNA against patients with T790M-positive EGFR-mutant NSCLC receiving osimertinib
title_full Predictive significance of circulating tumor DNA against patients with T790M-positive EGFR-mutant NSCLC receiving osimertinib
title_fullStr Predictive significance of circulating tumor DNA against patients with T790M-positive EGFR-mutant NSCLC receiving osimertinib
title_full_unstemmed Predictive significance of circulating tumor DNA against patients with T790M-positive EGFR-mutant NSCLC receiving osimertinib
title_short Predictive significance of circulating tumor DNA against patients with T790M-positive EGFR-mutant NSCLC receiving osimertinib
title_sort predictive significance of circulating tumor dna against patients with t790m-positive egfr-mutant nsclc receiving osimertinib
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10682450/
https://www.ncbi.nlm.nih.gov/pubmed/38012343
http://dx.doi.org/10.1038/s41598-023-48210-5
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