Open AccessMonitoring EGFR T790M with plasma DNA from lung cancer patients in a prospective observational study
Author(s) -
SueokaAragane Naoko,
Katakami Nobuyuki,
Satouchi Miyako,
Yokota Soichiro,
Aoe Keisuke,
Iwanaga Kentaro,
Otsuka Kojiro,
Morita Satoshi,
Kimura Shinya,
Negoro Shunichi
Publication year - 2016
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12847
Subject(s) - t790m , lung cancer , liquid biopsy , medicine , oncology , cancer , gefitinib , cancer research , pathology , epidermal growth factor receptor
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.