The ratio of T790M to EGFR-activating mutation predicts response of osimertinib in 1st or 2nd generation EGFR-TKI-refractory NSCLC

The ratio of T790M to EGFR-activating mutation predicts response of osimertinib in 1st or 2nd generation EGFR-TKI-refractory NSCLC

Abstract The most frequent mechanism of resistance after 1st/2nd-generation (G) epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is secondary point mutation Thr790Met (T790M) in EGFR. Afatinib followed by osimertinib (Afa group) may provide better outcomes for T790M-positive...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Motohiro Tamiya, Akihiro Tamiya, Norio Okamoto, Yoshihiko Taniguchi, Kazumi Nishino, Shinji Atagi, Tomonori Hirashima, Fumio Imamura, Toru Kumagai, Hidekazu Suzuki
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
Materias:
Medicine
R
Science
Q
Acceso en línea:https://doaj.org/article/971c6d6d531f455c899f4cb3858135b3
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:971c6d6d531f455c899f4cb3858135b3
record_format dspace
spelling oai:doaj.org-article:971c6d6d531f455c899f4cb3858135b32021-12-02T14:42:52ZThe ratio of T790M to EGFR-activating mutation predicts response of osimertinib in 1st or 2nd generation EGFR-TKI-refractory NSCLC10.1038/s41598-021-89006-92045-2322https://doaj.org/article/971c6d6d531f455c899f4cb3858135b32021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89006-9https://doaj.org/toc/2045-2322Abstract The most frequent mechanism of resistance after 1st/2nd-generation (G) epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is secondary point mutation Thr790Met (T790M) in EGFR. Afatinib followed by osimertinib (Afa group) may provide better outcomes for T790M-positive non-small cell lung cancer (NSCLC) than 1st-G EGFR-TKI followed by osimertinib (1st-G group). We studied 111 consecutive NSCLC patients with T790M mutation treated with osimertinib after progression following 1st/2nd-G EGFR-TKI between March 28, 2016 and March 31, 2018. We analyzed the ratio of T790M to EGFR-activating mutation (T790M ratio) in post EGFR-TKI resistance re-biopsy tissue using droplet digital polymerase chain reaction. And investigated whether afatinib purified the T790M mutation more than 1st-G EGFR-TKI. Among 60 patients with preserved re-biopsy tissue, we analyzed 38 having adequate DNA content. The response rate in Afa group was 81.8% (n = 11) and 1st-G group was 85.2% (n = 27). The mean T790M ratio in total population was 0.3643. The ratio in those with response to osimertinib was significantly higher than in the non-responders (0.395, 0.202; p = 0.0231) and was similar in Afa and 1st-G group (0.371, 0.362; p = 0.9693). T790M ratio significantly correlated with osimertinib response and was similar between the 1st/2nd-G EGFR-TKIs in 1st/2nd-G EGFR-TKI-refractory tumors.Motohiro TamiyaAkihiro TamiyaNorio OkamotoYoshihiko TaniguchiKazumi NishinoShinji AtagiTomonori HirashimaFumio ImamuraToru KumagaiHidekazu SuzukiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-7 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Motohiro Tamiya
Akihiro Tamiya
Norio Okamoto
Yoshihiko Taniguchi
Kazumi Nishino
Shinji Atagi
Tomonori Hirashima
Fumio Imamura
Toru Kumagai
Hidekazu Suzuki
The ratio of T790M to EGFR-activating mutation predicts response of osimertinib in 1st or 2nd generation EGFR-TKI-refractory NSCLC
description Abstract The most frequent mechanism of resistance after 1st/2nd-generation (G) epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is secondary point mutation Thr790Met (T790M) in EGFR. Afatinib followed by osimertinib (Afa group) may provide better outcomes for T790M-positive non-small cell lung cancer (NSCLC) than 1st-G EGFR-TKI followed by osimertinib (1st-G group). We studied 111 consecutive NSCLC patients with T790M mutation treated with osimertinib after progression following 1st/2nd-G EGFR-TKI between March 28, 2016 and March 31, 2018. We analyzed the ratio of T790M to EGFR-activating mutation (T790M ratio) in post EGFR-TKI resistance re-biopsy tissue using droplet digital polymerase chain reaction. And investigated whether afatinib purified the T790M mutation more than 1st-G EGFR-TKI. Among 60 patients with preserved re-biopsy tissue, we analyzed 38 having adequate DNA content. The response rate in Afa group was 81.8% (n = 11) and 1st-G group was 85.2% (n = 27). The mean T790M ratio in total population was 0.3643. The ratio in those with response to osimertinib was significantly higher than in the non-responders (0.395, 0.202; p = 0.0231) and was similar in Afa and 1st-G group (0.371, 0.362; p = 0.9693). T790M ratio significantly correlated with osimertinib response and was similar between the 1st/2nd-G EGFR-TKIs in 1st/2nd-G EGFR-TKI-refractory tumors.
format article
author Motohiro Tamiya
Akihiro Tamiya
Norio Okamoto
Yoshihiko Taniguchi
Kazumi Nishino
Shinji Atagi
Tomonori Hirashima
Fumio Imamura
Toru Kumagai
Hidekazu Suzuki
author_facet Motohiro Tamiya
Akihiro Tamiya
Norio Okamoto
Yoshihiko Taniguchi
Kazumi Nishino
Shinji Atagi
Tomonori Hirashima
Fumio Imamura
Toru Kumagai
Hidekazu Suzuki
author_sort Motohiro Tamiya
title The ratio of T790M to EGFR-activating mutation predicts response of osimertinib in 1st or 2nd generation EGFR-TKI-refractory NSCLC
title_short The ratio of T790M to EGFR-activating mutation predicts response of osimertinib in 1st or 2nd generation EGFR-TKI-refractory NSCLC
title_full The ratio of T790M to EGFR-activating mutation predicts response of osimertinib in 1st or 2nd generation EGFR-TKI-refractory NSCLC
title_fullStr The ratio of T790M to EGFR-activating mutation predicts response of osimertinib in 1st or 2nd generation EGFR-TKI-refractory NSCLC
title_full_unstemmed The ratio of T790M to EGFR-activating mutation predicts response of osimertinib in 1st or 2nd generation EGFR-TKI-refractory NSCLC
title_sort ratio of t790m to egfr-activating mutation predicts response of osimertinib in 1st or 2nd generation egfr-tki-refractory nsclc
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/971c6d6d531f455c899f4cb3858135b3
work_keys_str_mv AT motohirotamiya theratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
AT akihirotamiya theratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
AT noriookamoto theratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
AT yoshihikotaniguchi theratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
AT kazuminishino theratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
AT shinjiatagi theratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
AT tomonorihirashima theratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
AT fumioimamura theratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
AT torukumagai theratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
AT hidekazusuzuki theratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
AT motohirotamiya ratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
AT akihirotamiya ratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
AT noriookamoto ratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
AT yoshihikotaniguchi ratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
AT kazuminishino ratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
AT shinjiatagi ratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
AT tomonorihirashima ratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
AT fumioimamura ratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
AT torukumagai ratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
AT hidekazusuzuki ratiooft790mtoegfractivatingmutationpredictsresponseofosimertinibin1stor2ndgenerationegfrtkirefractorynsclc
_version_ 1718389583589146624

Ejemplares similares