TY - JOUR
T1 - CtDNA determination of EGFR mutation status in European and Japanese patients with advanced NSCLC
T2 - The ASSESS study
AU - Reck, Martin
AU - Hagiwara, Koichi
AU - Han, Baohui
AU - Tjulandin, Sergei
AU - Grohé, Christian
AU - Yokoi, Takashi
AU - Morabito, Alessandro
AU - Novello, Silvia
AU - Arriola, Edurne
AU - Molinier, Olivier
AU - McCormack, Rose
AU - Ratcliffe, Marianne
AU - Normanno, Nicola
PY - 2016
Y1 - 2016
N2 - Introduction: To offer patients with EGFR mutation- positive advanced NSCLC appropriate EGFR tyrosine kinase inhibitor treatment, mutation testing of tumor samples is required. However, tissue/cytologic samples are not always available or evaluable. The large, noninterventional diagnostic ASSESS study (NCT01785888) evaluated the utility of circulating free tumor-derived DNA (ctDNA) from plasma for EGFR mutation testing. Methods: ASSESS was conducted in 56 centers (in Europe and Japan). Eligible patients (with newly diagnosed locally advanced/metastatic treatment-naive advanced NSCLC) provided diagnostic tissue/cytologic and plasma samples. DNA extracted from tissue/cytologic samples was subjected to EGFR mutation testing using local practices; designated laboratories performed DNA extraction/mutation testing of blood samples. The primary end point was level of concordance of EGFR mutation status between matched tissue/cytologic and plasma samples. Results: Of 1311 patients enrolled, 1288 were eligible. Concordance ofmutation status in 1162matched sampleswas 89% (sensitivity 46%, specificity 97%, positive predictive value 78%, and negative predictive value 90%). A group of 25 patients with apparent false-positive plasma results was overrepresented for cytologic samples, use of less sensitive tissue testing methodologies, and smoking habits associated with high EGFR mutation frequency, indicative of falsenegative tumor results. In cases in which plasma and tumor samples were tested with identical highly sensitive methods, positive predictive value/sensitivitywere generally improved. Conclusions: These real-world data suggest that ctDNA is a feasible sample for EGFR mutation analysis. It is important to conduct mutation testing of both tumor and plasma samples in specialized laboratories, using robust/sensitive methods to ensure that patients receive appropriate treatments that target the molecular features of their disease.
AB - Introduction: To offer patients with EGFR mutation- positive advanced NSCLC appropriate EGFR tyrosine kinase inhibitor treatment, mutation testing of tumor samples is required. However, tissue/cytologic samples are not always available or evaluable. The large, noninterventional diagnostic ASSESS study (NCT01785888) evaluated the utility of circulating free tumor-derived DNA (ctDNA) from plasma for EGFR mutation testing. Methods: ASSESS was conducted in 56 centers (in Europe and Japan). Eligible patients (with newly diagnosed locally advanced/metastatic treatment-naive advanced NSCLC) provided diagnostic tissue/cytologic and plasma samples. DNA extracted from tissue/cytologic samples was subjected to EGFR mutation testing using local practices; designated laboratories performed DNA extraction/mutation testing of blood samples. The primary end point was level of concordance of EGFR mutation status between matched tissue/cytologic and plasma samples. Results: Of 1311 patients enrolled, 1288 were eligible. Concordance ofmutation status in 1162matched sampleswas 89% (sensitivity 46%, specificity 97%, positive predictive value 78%, and negative predictive value 90%). A group of 25 patients with apparent false-positive plasma results was overrepresented for cytologic samples, use of less sensitive tissue testing methodologies, and smoking habits associated with high EGFR mutation frequency, indicative of falsenegative tumor results. In cases in which plasma and tumor samples were tested with identical highly sensitive methods, positive predictive value/sensitivitywere generally improved. Conclusions: These real-world data suggest that ctDNA is a feasible sample for EGFR mutation analysis. It is important to conduct mutation testing of both tumor and plasma samples in specialized laboratories, using robust/sensitive methods to ensure that patients receive appropriate treatments that target the molecular features of their disease.
KW - CtDNA
KW - EGFR mutation
KW - NSCLC
KW - Plasma
KW - Realworld
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U2 - 10.1016/j.jtho.2016.05.036
DO - 10.1016/j.jtho.2016.05.036
M3 - Article
AN - SCOPUS:84991067898
VL - 11
SP - 1682
EP - 1689
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
SN - 1556-0864
IS - 10
ER -