In:
Cancer Science, Wiley, Vol. 107, No. 2 ( 2016-02), p. 162-167
Abstract:
Use of plasma DNA to detect mutations has spread widely as a form of liquid biopsy. EGFR T790M has been observed in half of lung cancer patients who have acquired resistance to EGFR tyrosine kinase inhibitors ( EGFR ‐ TKI ). Effectiveness of monitoring T790M via plasma DNA during treatment with EGFR ‐ TKI has not been established as an alternative to re‐biopsy. This was a prospective multicenter observational study involving non‐small cell lung cancer patients carrying EGFR L858R or exon 19 deletions, treated with EGFR ‐ TKI . The primary objective was to determine whether T790M could be detected using plasma DNA in patients with progressive disease ( PD ). T790M was examined using the mutation‐biased PCR and quenching probe ( MBP ‐ QP ) method, a sensitive, fully‐automated system developed in our laboratory. Eighty‐nine non‐small cell lung cancer patients were enrolled from seven hospitals in Japan. Sequential examinations revealed T790M in plasma DNA among 40% of patients who developed PD . Activating mutations, such as L858R and exon 19 deletions, were detected in 40% of patients using plasma DNA , and either T790M or activating mutations were observed in 62%. Dividing into four periods (before PD , at PD , at discontinuation of EGFR ‐ TKI and subsequently), T790M was detected in 10, 19, 24 and 27% of patients, respectively. Smokers, males, patients having exon 19 deletions and patients who developed new lesions evidenced significantly frequent presence of T790M in plasma DNA . Monitoring T790M with plasma DNA using MBP ‐ QP reflects the clinical course of lung cancer patients treated with EGFR ‐ TKI . Detection of T790M with plasma DNA was correlated with EGFR mutation type, exon 19 deletions and tumor progression. Re‐biopsy could be performed only in 14% of PD cases, suggesting difficulty in obtaining re‐biopsy specimens in practice. Monitoring T790M with plasma DNA reflects the clinical course, and is potentially useful in designing strategies for subsequent treatment.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2016.107.issue-2
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
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