PMID- 31097094
OWN - NLM
STAT- MEDLINE
DCOM- 20200407
LR  - 20220603
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 132
DP  - 2019 Jun
TI  - Re-administration of osimertinib in osimertinib-acquired resistant non-small-cell 
      lung cancer.
PG  - 54-58
LID - S0169-5002(19)30337-X [pii]
LID - 10.1016/j.lungcan.2019.02.021 [doi]
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.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Ichihara, Eiki
AU  - Ichihara E
AD  - Department of Allergy and Respiratory Medicine, Okayama University Hospital, 
      Okayama, Japan. Electronic address: ichiha-e@md.okayama-u.ac.jp.
FAU - Hotta, Katsuyuki
AU  - Hotta K
AD  - Department of Allergy and Respiratory Medicine, Okayama University Hospital, 
      Okayama, Japan; Center for Innovative Clinical Medicine, Okayama University 
      Hospital, Okayama, Japan.
FAU - Ninomiya, Kiichiro
AU  - Ninomiya K
AD  - Department of Allergy and Respiratory Medicine, Okayama University Hospital, 
      Okayama, Japan.
FAU - Kubo, Toshio
AU  - Kubo T
AD  - Center for Clinical Oncology, Okayama University Hospital, Okayama, Japan.
FAU - Ohashi, Kadoaki
AU  - Ohashi K
AD  - Department of Allergy and Respiratory Medicine, Okayama University Hospital, 
      Okayama, Japan.
FAU - Rai, Kammei
AU  - Rai K
AD  - Department of Allergy and Respiratory Medicine, Okayama University Hospital, 
      Okayama, Japan.
FAU - Tanaka, Hisaaki
AU  - Tanaka H
AD  - Department of Respiratory Medicine, National Hospital Organization Minami-Okayama 
      Medical Center, Japan.
FAU - Tabata, Masahiro
AU  - Tabata M
AD  - Center for Clinical Oncology, Okayama University Hospital, Okayama, Japan.
FAU - Maeda, Yoshinobu
AU  - Maeda Y
AD  - Department of Hematology, Oncology and Respiratory Medicine, Okayama University 
      Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 
      Japan.
FAU - Kiura, Katsuyuki
AU  - Kiura K
AD  - Department of Allergy and Respiratory Medicine, Okayama University Hospital, 
      Okayama, Japan.
LA  - eng
PT  - Journal Article
DEP - 20190406
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Acrylamides)
RN  - 0 (Aniline Compounds)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 3C06JJ0Z2O (osimertinib)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Acrylamides/*therapeutic use
MH  - Adult
MH  - Aged
MH  - Aniline Compounds/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/mortality
MH  - Drug Resistance, Neoplasm/genetics
MH  - ErbB Receptors/antagonists & inhibitors/genetics
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/genetics/mortality
MH  - Male
MH  - Middle Aged
MH  - Mutation/genetics
MH  - Neoplasm Staging
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Survival Analysis
OTO - NOTNLM
OT  - EGFR TKI
OT  - EGFR mutation
OT  - Non-small-cell lung cancer
OT  - Osimertinib
OT  - Re-administration
OT  - T790M
EDAT- 2019/05/18 06:00
MHDA- 2020/04/09 06:00
CRDT- 2019/05/18 06:00
PHST- 2018/10/22 00:00 [received]
PHST- 2019/02/06 00:00 [revised]
PHST- 2019/02/19 00:00 [accepted]
PHST- 2019/05/18 06:00 [entrez]
PHST- 2019/05/18 06:00 [pubmed]
PHST- 2020/04/09 06:00 [medline]
AID - S0169-5002(19)30337-X [pii]
AID - 10.1016/j.lungcan.2019.02.021 [doi]
PST - ppublish
SO  - Lung Cancer. 2019 Jun;132:54-58. doi: 10.1016/j.lungcan.2019.02.021. Epub 2019 
      Apr 6.