Re-administration of osimertinib in osimertinib-acquired resistant non-small-cell lung cancer

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Abstract

Background: Osimertinib is a tyrosine kinase inhibitor (TKI) that is an essential agent for the treatment of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). However, there is no established strategy for treatment following acquired resistance to this agent. One potential strategy for treating acquired resistance to EGFR TKIs is re-administration, which has been evaluated mainly using first- or second-generation EGFR TKIs. However, no clinical data are available with which to determine the significance of re-administration of osimertinib, a third-generation EGFR TKI. The aim of this study was to evaluate the efficacy of re-administering osimertinib to patients who had acquired resistance to this agent. Patients and methods: We reviewed the medical records of consecutive patients with advanced NSCLC harboring EGFR-activating mutations and secondary T790M, who had undergone osimertinib re-administration to treat acquired resistance. Results: Seventeen patients were re-administered osimertinib after acquiring resistance to osimertinib. Of these, two received osimertinib to treat carcinomatous meningitis without any measurable lesion. Responses were evaluated in the remaining 15 patients. The objective response and disease control rates were 33% and 73%, respectively. Tumor shrinkage by osimertinib re-administration was associated with that due to initial osimertinib treatment (r = 0.585, 95% confidence interval [CI]: 0.104–0.844). In the remaining two patients without measurable lesions, one exhibited improved clinical symptoms following osimertinib re-administration. The median progression-free survival (PFS) time of all 17 patients was 4.1 months (95% CI: 1.9–6.7). The toxicity of re-administration was low, without interruption of the treatment due to adverse events (AEs). Most patients had grade 2 AEs or lower. Conclusions: Re-administration of osimertinib for EGFR-mutant NSCLC yielded modest activity with tolerable toxicity.

Original languageEnglish
Pages (from-to)54-58
Number of pages5
JournalLung Cancer
Volume132
DOIs
Publication statusPublished - Jun 1 2019

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Non-Small Cell Lung Carcinoma
Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
osimertinib
Meningeal Carcinomatosis
Confidence Intervals
Therapeutics
Disease-Free Survival
Medical Records
Mutation

Keywords

  • EGFR mutation
  • EGFR TKI
  • Non-small-cell lung cancer
  • Osimertinib
  • Re-administration
  • T790M

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

@article{38c12ed4ab0a4b92a1e8a773dc21078b,
title = "Re-administration of osimertinib in osimertinib-acquired resistant non-small-cell lung cancer",
abstract = "Background: Osimertinib is a tyrosine kinase inhibitor (TKI) that is an essential agent for the treatment of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). However, there is no established strategy for treatment following acquired resistance to this agent. One potential strategy for treating acquired resistance to EGFR TKIs is re-administration, which has been evaluated mainly using first- or second-generation EGFR TKIs. However, no clinical data are available with which to determine the significance of re-administration of osimertinib, a third-generation EGFR TKI. The aim of this study was to evaluate the efficacy of re-administering osimertinib to patients who had acquired resistance to this agent. Patients and methods: We reviewed the medical records of consecutive patients with advanced NSCLC harboring EGFR-activating mutations and secondary T790M, who had undergone osimertinib re-administration to treat acquired resistance. Results: Seventeen patients were re-administered osimertinib after acquiring resistance to osimertinib. Of these, two received osimertinib to treat carcinomatous meningitis without any measurable lesion. Responses were evaluated in the remaining 15 patients. The objective response and disease control rates were 33{\%} and 73{\%}, respectively. Tumor shrinkage by osimertinib re-administration was associated with that due to initial osimertinib treatment (r = 0.585, 95{\%} confidence interval [CI]: 0.104–0.844). In the remaining two patients without measurable lesions, one exhibited improved clinical symptoms following osimertinib re-administration. The median progression-free survival (PFS) time of all 17 patients was 4.1 months (95{\%} CI: 1.9–6.7). The toxicity of re-administration was low, without interruption of the treatment due to adverse events (AEs). Most patients had grade 2 AEs or lower. Conclusions: Re-administration of osimertinib for EGFR-mutant NSCLC yielded modest activity with tolerable toxicity.",
keywords = "EGFR mutation, EGFR TKI, Non-small-cell lung cancer, Osimertinib, Re-administration, T790M",
author = "Eiki Ichihara and Katsuyuki Hotta and Kiichiro Ninomiya and Toshio Kubo and Kadoaki Oohashi and Kanmei Rai and Hisaaki Tanaka and Masahiro Tabata and Yoshinobu Maeda and Katsuyuki Kiura",
year = "2019",
month = "6",
day = "1",
doi = "10.1016/j.lungcan.2019.02.021",
language = "English",
volume = "132",
pages = "54--58",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",

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TY - JOUR

T1 - Re-administration of osimertinib in osimertinib-acquired resistant non-small-cell lung cancer

AU - Ichihara, Eiki

AU - Hotta, Katsuyuki

AU - Ninomiya, Kiichiro

AU - Kubo, Toshio

AU - Oohashi, Kadoaki

AU - Rai, Kanmei

AU - Tanaka, Hisaaki

AU - Tabata, Masahiro

AU - Maeda, Yoshinobu

AU - Kiura, Katsuyuki

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Background: Osimertinib is a tyrosine kinase inhibitor (TKI) that is an essential agent for the treatment of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). However, there is no established strategy for treatment following acquired resistance to this agent. One potential strategy for treating acquired resistance to EGFR TKIs is re-administration, which has been evaluated mainly using first- or second-generation EGFR TKIs. However, no clinical data are available with which to determine the significance of re-administration of osimertinib, a third-generation EGFR TKI. The aim of this study was to evaluate the efficacy of re-administering osimertinib to patients who had acquired resistance to this agent. Patients and methods: We reviewed the medical records of consecutive patients with advanced NSCLC harboring EGFR-activating mutations and secondary T790M, who had undergone osimertinib re-administration to treat acquired resistance. Results: Seventeen patients were re-administered osimertinib after acquiring resistance to osimertinib. Of these, two received osimertinib to treat carcinomatous meningitis without any measurable lesion. Responses were evaluated in the remaining 15 patients. The objective response and disease control rates were 33% and 73%, respectively. Tumor shrinkage by osimertinib re-administration was associated with that due to initial osimertinib treatment (r = 0.585, 95% confidence interval [CI]: 0.104–0.844). In the remaining two patients without measurable lesions, one exhibited improved clinical symptoms following osimertinib re-administration. The median progression-free survival (PFS) time of all 17 patients was 4.1 months (95% CI: 1.9–6.7). The toxicity of re-administration was low, without interruption of the treatment due to adverse events (AEs). Most patients had grade 2 AEs or lower. Conclusions: Re-administration of osimertinib for EGFR-mutant NSCLC yielded modest activity with tolerable toxicity.

AB - Background: Osimertinib is a tyrosine kinase inhibitor (TKI) that is an essential agent for the treatment of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). However, there is no established strategy for treatment following acquired resistance to this agent. One potential strategy for treating acquired resistance to EGFR TKIs is re-administration, which has been evaluated mainly using first- or second-generation EGFR TKIs. However, no clinical data are available with which to determine the significance of re-administration of osimertinib, a third-generation EGFR TKI. The aim of this study was to evaluate the efficacy of re-administering osimertinib to patients who had acquired resistance to this agent. Patients and methods: We reviewed the medical records of consecutive patients with advanced NSCLC harboring EGFR-activating mutations and secondary T790M, who had undergone osimertinib re-administration to treat acquired resistance. Results: Seventeen patients were re-administered osimertinib after acquiring resistance to osimertinib. Of these, two received osimertinib to treat carcinomatous meningitis without any measurable lesion. Responses were evaluated in the remaining 15 patients. The objective response and disease control rates were 33% and 73%, respectively. Tumor shrinkage by osimertinib re-administration was associated with that due to initial osimertinib treatment (r = 0.585, 95% confidence interval [CI]: 0.104–0.844). In the remaining two patients without measurable lesions, one exhibited improved clinical symptoms following osimertinib re-administration. The median progression-free survival (PFS) time of all 17 patients was 4.1 months (95% CI: 1.9–6.7). The toxicity of re-administration was low, without interruption of the treatment due to adverse events (AEs). Most patients had grade 2 AEs or lower. Conclusions: Re-administration of osimertinib for EGFR-mutant NSCLC yielded modest activity with tolerable toxicity.

KW - EGFR mutation

KW - EGFR TKI

KW - Non-small-cell lung cancer

KW - Osimertinib

KW - Re-administration

KW - T790M

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U2 - 10.1016/j.lungcan.2019.02.021

DO - 10.1016/j.lungcan.2019.02.021

M3 - Article

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EP - 58

JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

ER -