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 - Ohashi, Kadoaki
AU - Rai, Kanmei
AU - Tanaka, Hisaaki
AU - Tabata, Masahiro
AU - Maeda, Yoshinobu
AU - Kiura, Katsuyuki
N1 - Funding Information:
EI received honoraria from AstraZeneca, Eli Lilly Japan, Boehringer Ingelheim, and Chugai Pharmaceutical. EI received additional research funding from Eli Lilly Japan and MSD. KH received honoraria from AstraZeneca, Eli Lilly Japan, Daiichi Sankyo Pharmaceutical, Boehringer Ingelheim, Nihon Kayaku, Taiho Pharmaceutical, Chugai Pharmaceutical, and Sanofi Aventis. KH received additional research funding from Eli Lilly Japan, MSD, and Chugai Pharmaceutical. All other authors declare no conflicts of interest regarding this study. TM received honoraria from Takeda Pharmaceutical, Kyowa Hakko Kirin, Chugai Pharmaceutical, Novartis Pharmaceutical, Otsuka Pharmaceutical, Astellas Pharmaceutical, AsahiKASEI, Sumitomo Dainippon Pharmaceutical, from Mochida Pharmaceutical, Bristol–Myers Squibb, Phizer, Nippon Shinyaku, Janssen Pharmaceutical, Celgene, Eisai, Mundipharma, and Meiji Seika Pharma. TM also received research funding from Akeda Pharmaceutical and Kyowa Hakko Kirin. KO received research grants from Boehringer Ingelheim and Novartis Pharmaceuticals, Japan. KK received honoraria from Eli Lilly Japan, Nihon Kayaku, AstraZeneca, Daiichi Sankyo Pharmaceuticals, Chugai Pharmaceuticals, Taiho Pharmaceuticals, Boehringer Ingelheim, and Sanofi Aventis.
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/6
Y1 - 2019/6
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 TKI
KW - EGFR mutation
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
C2 - 31097094
AN - SCOPUS:85064267522
VL - 132
SP - 54
EP - 58
JO - Lung Cancer
JF - Lung Cancer
SN - 0169-5002
ER -
