Eiki Ichihara1, Katsuyuki Hotta2, Kiichiro Ninomiya3, Toshio Kubo4, Kadoaki Ohashi3, Kammei Rai3, Hisaaki Tanaka5, Masahiro Tabata4, Yoshinobu Maeda6, Katsuyuki Kiura3. 1. Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan. Electronic address: ichiha-e@md.okayama-u.ac.jp. 2. Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan; Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan. 3. Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan. 4. Center for Clinical Oncology, Okayama University Hospital, Okayama, Japan. 5. Department of Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center, Japan. 6. Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
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.
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.
Authors: A Cortellini; A Leonetti; A Catino; P Pizzutillo; B Ricciuti; A De Giglio; R Chiari; P Bordi; D Santini; R Giusti; M De Tursi; D Brocco; F Zoratto; F Rastelli; F Citarella; M Russano; M Filetti; P Marchetti; R Berardi; M Torniai; D Cortinovis; E Sala; C Maggioni; A Follador; M Macerelli; O Nigro; A Tuzi; D Iacono; M R Migliorino; G Banna; G Porzio; K Cannita; M G Ferrara; E Bria; D Galetta; C Ficorella; M Tiseo Journal: Clin Transl Oncol Date: 2019-08-07 Impact factor: 3.405
Authors: Shaocong Wu; Min Luo; Kenneth K W To; Jianye Zhang; Chaoyue Su; Hong Zhang; Sainan An; Fang Wang; Da Chen; Liwu Fu Journal: Mol Cancer Date: 2021-01-18 Impact factor: 27.401