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Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity
DC Field | Value | Language |
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dc.contributor.author | Ballard, Peter | - |
dc.contributor.author | Yates, James W. T. | - |
dc.contributor.author | Yang, Zhenfan | - |
dc.contributor.author | Kim, Dong-Wan | - |
dc.contributor.author | Yang, James Chih-Hsin | - |
dc.contributor.author | Cantarini, Mireille | - |
dc.contributor.author | Pickup, Kathryn | - |
dc.contributor.author | Jordan, Angela | - |
dc.contributor.author | Hickey, Mike | - |
dc.contributor.author | Grist, Matthew | - |
dc.contributor.author | Box, Matthew | - |
dc.contributor.author | Johnstrom, Peter | - |
dc.contributor.author | Varnas, Katarina | - |
dc.contributor.author | Malmquist, Jonas | - |
dc.contributor.author | Thress, Kenneth S. | - |
dc.contributor.author | Janne, Pasi A. | - |
dc.contributor.author | Cross, Darren | - |
dc.date.accessioned | 2020-04-27T11:11:41Z | - |
dc.date.available | 2020-04-27T11:11:41Z | - |
dc.date.created | 2018-09-07 | - |
dc.date.issued | 2016-10 | - |
dc.identifier.citation | Clinical Cancer Research, Vol.22 No.20, pp.5130-5140 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.other | 51919 | - |
dc.identifier.uri | https://hdl.handle.net/10371/165281 | - |
dc.description.abstract | Purpose: Approximately one-third of patients with non-small cell lung cancer (NSCLC) harboring tumors with EGFR-tyrosine kinase inhibitor (TKI)-sensitizing mutations (EGFRm) experience disease progression during treatment due to brain metastases. Despite anecdotal reports of EGFR-TKIs providing benefit in some patients with EGFRm NSCLC brain metastases, there is a clinical need for novel EGFR-TKIs with improved efficacy against brain lesions. Experimental Design: We performed preclinical assessments of brain penetration and activity of osimertinib (AZD9291), an oral, potent, irreversible EGFR-TKI selective for EGFRm and T790M resistance mutations, and other EGFR-TKIs in various animal models of EGFR-mutant NSCLC brain metastases. We also present case reports of previously treated patients with EGFRm-advanced NSCLC and brain metastases who received osimertinib in the phase I/II AURA study (NCT01802632). Results: Osimertinib demonstrated greater penetration of the mouse blood-brain barrier than gefitinib, rociletinib (CO-1686), or afatinib, and at clinically relevant doses induced sustained tumor regression in an EGFRm PC9 mouse brain metastases model; rociletinib did not achieve tumor regression. Under positron emission tomography micro-dosing conditions, [C-11] osimertinib showed markedly greater exposure in the cynomolgus monkey brain than [C-11] rociletinib and [C-11] gefitinib. Early clinical evidence of osimertinib activity in previously treated patients with EGFRm-advanced NSCLC and brain metastases is also reported. Conclusions: Osimertinib may represent a clinically significant treatment option for patients with EGFRm NSCLC and brain metastases. Further investigation of osimertinib in this patient population is ongoing. (C) 2016 AACR. | - |
dc.language | 영어 | - |
dc.publisher | American Association for Cancer Research | - |
dc.title | Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 김동완 | - |
dc.identifier.doi | 10.1158/1078-0432.CCR-16-0399 | - |
dc.citation.journaltitle | Clinical Cancer Research | - |
dc.identifier.wosid | 000385632700021 | - |
dc.identifier.scopusid | 2-s2.0-84991730676 | - |
dc.citation.endpage | 5140 | - |
dc.citation.number | 20 | - |
dc.citation.startpage | 5130 | - |
dc.citation.volume | 22 | - |
dc.identifier.sci | 000385632700021 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Kim, Dong-Wan | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | CELL LUNG-CANCER | - |
dc.subject.keywordPlus | TYROSINE KINASE INHIBITOR | - |
dc.subject.keywordPlus | UNBOUND BRAIN | - |
dc.subject.keywordPlus | GEFITINIB | - |
dc.subject.keywordPlus | ERLOTINIB | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | PET | - |
dc.subject.keywordPlus | BARRIER | - |
dc.subject.keywordPlus | DISEASE | - |
dc.subject.keywordPlus | CHEMOTHERAPY | - |
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