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Optimizing Sequential Treatment With EGFR Tyrosine Kinase Inhibitor With a Simulation of the T790M Mutation Rate in EGFR–Mutated Lung Cancer

INTRODUCTION: The mutation rate of T790M might change the effective therapeutic sequence of EGFR tyrosine kinase inhibitors (TKIs). This simulation estimates the T790M positivity rate required for first-line first- or second-generation EGFR TKI to exceed overall progression-free survival (PFS) of fi...

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Autores principales: Haratake, Naoki, Misumi, Toshihiro, Yamanaka, Takeharu, Seto, Takashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474446/
https://www.ncbi.nlm.nih.gov/pubmed/34589964
http://dx.doi.org/10.1016/j.jtocrr.2020.100085
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author Haratake, Naoki
Misumi, Toshihiro
Yamanaka, Takeharu
Seto, Takashi
author_facet Haratake, Naoki
Misumi, Toshihiro
Yamanaka, Takeharu
Seto, Takashi
author_sort Haratake, Naoki
collection PubMed
description INTRODUCTION: The mutation rate of T790M might change the effective therapeutic sequence of EGFR tyrosine kinase inhibitors (TKIs). This simulation estimates the T790M positivity rate required for first-line first- or second-generation EGFR TKI to exceed overall progression-free survival (PFS) of first-line osimertinib. METHODS: The PFS of each treatment with EGFR TKIs as first-line treatment, with osimertinib as second-line treatment among T790M-positive cases, and chemotherapy as second-line treatment among T790M-negative cases was set based on phase 3 trials. Overall PFS A of “upfront osimertinib” and overall PFS B of “first- or second-generation EGFR TKIs followed by osimertinib or chemotherapy” were simulated at different T790M mutation rates, to estimate the T790M mutation rate at which PFS B exceeds PFS A. RESULTS: Upfront osimertinib: In the setting of PFS of 19 months with first-line osimertinib, the median overall PFS A was 24.8 months (95% confidence interval [CI]: 21.6–28.0 mo). Upfront first- or second-generation EGFR TKI: When the T790M positivity rate was set to 50% and the PFS of second-line osimertinib was 10 months, the total median PFS (PFS B) was 20.2 months (95% CI: 17.5–22.9 mo). Even at a T790M mutation rate of 100%, PFS B (24.7 mo; 95% CI: 21.9–27.9 mo) was shorter than PFS A. CONCLUSIONS: Even with a T790M mutation rate of 100%, upfront osimertinib treatment is associated with better median PFS than the upfront treatment with first- or second-generation EGFR TKIs. Consistent with the results of the FLAURA trial, with regard to EGFR TKI monotherapy in the first-line treatment, upfront osimertinib would contribute to good prognosis.
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spelling pubmed-84744462021-09-28 Optimizing Sequential Treatment With EGFR Tyrosine Kinase Inhibitor With a Simulation of the T790M Mutation Rate in EGFR–Mutated Lung Cancer Haratake, Naoki Misumi, Toshihiro Yamanaka, Takeharu Seto, Takashi JTO Clin Res Rep Original Article INTRODUCTION: The mutation rate of T790M might change the effective therapeutic sequence of EGFR tyrosine kinase inhibitors (TKIs). This simulation estimates the T790M positivity rate required for first-line first- or second-generation EGFR TKI to exceed overall progression-free survival (PFS) of first-line osimertinib. METHODS: The PFS of each treatment with EGFR TKIs as first-line treatment, with osimertinib as second-line treatment among T790M-positive cases, and chemotherapy as second-line treatment among T790M-negative cases was set based on phase 3 trials. Overall PFS A of “upfront osimertinib” and overall PFS B of “first- or second-generation EGFR TKIs followed by osimertinib or chemotherapy” were simulated at different T790M mutation rates, to estimate the T790M mutation rate at which PFS B exceeds PFS A. RESULTS: Upfront osimertinib: In the setting of PFS of 19 months with first-line osimertinib, the median overall PFS A was 24.8 months (95% confidence interval [CI]: 21.6–28.0 mo). Upfront first- or second-generation EGFR TKI: When the T790M positivity rate was set to 50% and the PFS of second-line osimertinib was 10 months, the total median PFS (PFS B) was 20.2 months (95% CI: 17.5–22.9 mo). Even at a T790M mutation rate of 100%, PFS B (24.7 mo; 95% CI: 21.9–27.9 mo) was shorter than PFS A. CONCLUSIONS: Even with a T790M mutation rate of 100%, upfront osimertinib treatment is associated with better median PFS than the upfront treatment with first- or second-generation EGFR TKIs. Consistent with the results of the FLAURA trial, with regard to EGFR TKI monotherapy in the first-line treatment, upfront osimertinib would contribute to good prognosis. Elsevier 2020-08-21 /pmc/articles/PMC8474446/ /pubmed/34589964 http://dx.doi.org/10.1016/j.jtocrr.2020.100085 Text en © 2020 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Haratake, Naoki
Misumi, Toshihiro
Yamanaka, Takeharu
Seto, Takashi
Optimizing Sequential Treatment With EGFR Tyrosine Kinase Inhibitor With a Simulation of the T790M Mutation Rate in EGFR–Mutated Lung Cancer
title Optimizing Sequential Treatment With EGFR Tyrosine Kinase Inhibitor With a Simulation of the T790M Mutation Rate in EGFR–Mutated Lung Cancer
title_full Optimizing Sequential Treatment With EGFR Tyrosine Kinase Inhibitor With a Simulation of the T790M Mutation Rate in EGFR–Mutated Lung Cancer
title_fullStr Optimizing Sequential Treatment With EGFR Tyrosine Kinase Inhibitor With a Simulation of the T790M Mutation Rate in EGFR–Mutated Lung Cancer
title_full_unstemmed Optimizing Sequential Treatment With EGFR Tyrosine Kinase Inhibitor With a Simulation of the T790M Mutation Rate in EGFR–Mutated Lung Cancer
title_short Optimizing Sequential Treatment With EGFR Tyrosine Kinase Inhibitor With a Simulation of the T790M Mutation Rate in EGFR–Mutated Lung Cancer
title_sort optimizing sequential treatment with egfr tyrosine kinase inhibitor with a simulation of the t790m mutation rate in egfr–mutated lung cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474446/
https://www.ncbi.nlm.nih.gov/pubmed/34589964
http://dx.doi.org/10.1016/j.jtocrr.2020.100085
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