Abstract 5587: Serial monitoring of EGFR mutations in plasma and evaluation of EGFR mutation status in matched tissue and plasma from NSCLC patients treated with CO-1686
Background: We examined the detection of EGFR mutations in circulating free DNA from plasma and the concordance of EGFR mutation status between matched plasma and tumor tissue in a cohort of newly diagnosed or relapsed patients with advanced NSCLC. CO-1686 is an oral, potent, small-molecule irrevers...
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Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2014-10, Vol.74 (19_Supplement), p.5587-5587 |
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Sprache: | eng |
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Zusammenfassung: | Background: We examined the detection of EGFR mutations in circulating free DNA from plasma and the concordance of EGFR mutation status between matched plasma and tumor tissue in a cohort of newly diagnosed or relapsed patients with advanced NSCLC. CO-1686 is an oral, potent, small-molecule irreversible tyrosine kinase inhibitor that selectively targets mutant forms of EGFR, including T790M, L858R and Del(19), while sparing wild-type EGFR. Promising clinical activity has recently been reported from an on-going Phase I/II trial.
Methods: Matched tumor tissue and blood from 97 evaluable Stage IIIB/IV NSCLC patients, 40 treated with CO-1686, were tested using two allele-specific PCR assays, the cobas® EGFR FFPET and cobas® EGFR blood tests. Each test detects 41 mutations in EGFR, including the T790M resistance mutation, exon 19 deletions and L858R. In a subset of 30 patients, we compared the cobas plasma results to BEAMing, a highly quantitative and sensitive technology based on digital PCR. BEAMing was also used to serially monitor changes of the plasma EGFR mutation burden of several patients in response to CO-1686.
Results: Using tissue as the reference, the positive percent agreement between tissue and plasma was 73% (57/78) for activating mutations and 62% (21/34) for T790M. The cobas® EGFR blood test identified two patients with T790M mutations in plasma that were not detected in the corresponding tumor biopsy_likely because of tumor heterogeneity. The M0/M1a/M1b status was known for 73 EGFR mutation-positive patients. Of the 49 with extrathoracic metastatic disease (M1b), 43 were found to have an activating mutation in plasma (88%). Conversely, only 50% (12/24) of EGFR mutation-positive patients with intrathoracic metastatic disease (M0/M1a) had detectable activating mutations in plasma (p |
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ISSN: | 0008-5472 1538-7445 |
DOI: | 10.1158/1538-7445.AM2014-5587 |