Variations in EGFR ctDNA Correlates to the Clinica

Authors: Jinfeng He Wei Tan Xuelian Tang Jingping Ma

Publish Date: 2016/08/11

Volume: 23, Issue: 2, Pages: 307-315

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Abstract

Monitoring of non small cell lung cancer NSCLC patients on afatinib after acquired resistance to 1st generation tyrosine kinase inhibitors is important Circulating tumor DNA ctDNA offers an attractive means other than conventional tissue biopsy to characterize real time dynamic changes of the disease In our study we aim to ascertain the clinical value for ctDNA monitoring of NSCLC patients with acquired resistance for afatinib treatment 200 patients positive for the activating epithermal growth factor receptor EGFR mutations were recruited for the study Baseline molecular profiling for L858R Exon 19 deletion and T790M were performed Thereafter serial blood samples were taken and patients were assessed by overall survival OS to determine the usefulness of ctDNA monitoring At baseline matched tumor biopsy and ctDNA analysis had a concordance agreement of 935 for L858R and exon 19 deletion We also determined that a large proportion of patients had the drug resistance mutation T790M prior to starting afatinib and these patients were linked to a worse survival outcome For patients that registered a drop in ctDNA levels after afatinib was administered we observed that their survival outcome was more favorable hazard ratio 156 95 CI 104 to 243 ctDNA levels were mostly elevated after the 3rd sampling cycle Our results suggest that ctDNA can be used to predict the clinical benefits of afatinib treatment Pre and post blood sampling aids to identify patient groups that may benefit most from the treatment and ctDNA is relatively sensitive to address the dynamic changes of the disease at the molecular levelAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards

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