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 language | English |
|---|---|
| Pages (from-to) | 54-58 |
| Number of pages | 5 |
| Journal | Lung Cancer |
| Volume | 132 |
| DOIs | |
| Publication status | Published - Jun 1 2019 |
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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
Re-administration of osimertinib in osimertinib-acquired resistant non-small-cell lung cancer. / Ichihara, Eiki; Hotta, Katsuyuki; Ninomiya, Kiichiro; Kubo, Toshio; Oohashi, Kadoaki; Rai, Kanmei; Tanaka, Hisaaki; Tabata, Masahiro; Maeda, Yoshinobu; Kiura, Katsuyuki.
In: Lung Cancer, Vol. 132, 01.06.2019, p. 54-58.Research output: Contribution to journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=85064267522&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85064267522&partnerID=8YFLogxK
U2 - 10.1016/j.lungcan.2019.02.021
DO - 10.1016/j.lungcan.2019.02.021
M3 - Article
VL - 132
SP - 54
EP - 58
JO - Lung Cancer
JF - Lung Cancer
SN - 0169-5002
ER -