Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/16126
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dc.contributor.authorChia, Puey Ling-
dc.contributor.authorDo, Hongdo-
dc.contributor.authorMorey, Adrienne-
dc.contributor.authorMitchell, Paul L R-
dc.contributor.authorDobrovic, Alexander-
dc.contributor.authorJohn, Thomas-
dc.date2016-05-11-
dc.date.accessioned2016-08-15T05:44:16Z-
dc.date.available2016-08-15T05:44:16Z-
dc.date.issued2016-08-
dc.identifier.citationLung Cancer 2016; 98: 29-32en_US
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/16126-
dc.description.abstractAZD9291, a T790M specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has demonstrated impressive response rates in tumours harbouring the EGFR T790M resistance mutation. Emergence of resistance to AZD9291 has been shown to occur through several different mechanisms including the development of new mutations (e.g. C797S) in the EGFR tyrosine kinase domain. We studied two patients with paired tumour biopsies and blood samples pre- and post-progression on AZD9291 to explore possible resistance mechanisms. Pre- and Post-AZD9291 tumour biopsies as well as serial plasma samples were collected from two patients on the AURA clinical study (AZD9291 First Time in Patients Ascending Dose study). Droplet digital PCR (ddPCR) assays were used to quantify T790M, the driver EGFR mutation, and the C797S mutation in genomic DNA from paired tumour biopsies and plasma cell-free DNA. In the first patient, both EGFR T790M and L858R became undetectable in the plasma within 1 month after treatment with AZD9291. However, the T790M and the original L858R mutation re-emerged with radiologically confirmed resistance to AZD9291. In patient two, the levels of T790 M were undetectable at the time of radiological resistance to AZD9291 but increasing levels of the original EGFR exon 19 deletion was detected. MET amplification was detected in a biopsy performed on progression. The EGFR C797S mutation was not detected in either patient at the time of relapse. ddPCR of cell free DNA enables real time monitoring of patients on 3rd generation TKIs. As resistance mechanisms are variable, monitoring levels of the initial activating EGFR mutation may facilitate more reliable detection of progression.en_US
dc.titleTemporal changes of EGFR mutations and T790M levels in tumour and plasma DNA following AZD9291 treatmenten_US
dc.typeJournal Articleen_US
dc.identifier.journaltitleLung Canceren_US
dc.identifier.affiliationAustin Health, Heidelberg, Victoria, Australiaen_US
dc.identifier.affiliationDepartment of Medical Oncology, Austin Health, Heidelberg, Victoria, Australiaen_US
dc.identifier.affiliationOlivia Newton-John Cancer Research Institute, Austin Health, Heidelberg, Victoria, Australiaen_US
dc.identifier.affiliationTranslational Genomics and Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute, Austin Health, Heidelberg, Victoria, Australiaen_US
dc.identifier.affiliationDepartment of Pathology, University of Melbourne, Parkville, Victoria, Australiaen_US
dc.identifier.affiliationSchool of Cancer Medicine, La Trobe University, Bundoora, Victoria, Australiaen_US
dc.identifier.affiliationDepartment of Anatomical Pathology, St Vincent's Hospital, Sydney, Australiaen_US
dc.identifier.pubmedurihttps://pubmed.ncbi.nlm.nih.gov/27393503en_US
dc.identifier.doi10.1016/j.lungcan.2016.05.003en_US
dc.type.contentTexten_US
dc.identifier.orcid0000-0003-3414-112Xen_US
dc.type.austinJournal Articleen_US
local.name.researcherChia, Puey Ling
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.openairetypeJournal Article-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
crisitem.author.deptMedical Oncology-
crisitem.author.deptOlivia Newton-John Cancer Wellness and Research Centre-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
crisitem.author.deptSurgery (University of Melbourne)-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
crisitem.author.deptMedical Oncology-
crisitem.author.deptOlivia Newton-John Cancer Wellness and Research Centre-
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