title: ctDNA Determination of EGFR Mutation Status in European and Japanese Patients with Advanced NSCLC: The ASSESS Study.
abstract: 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.
  
  
  
  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.
  
  
  
  Of 1311 patients enrolled, 1288 were eligible. Concordance of mutation status in 1162 matched samples was 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 false-negative tumor results. In cases in which plasma and tumor samples were tested with identical highly sensitive methods, positive predictive value/sensitivity were generally improved.
  
  
  
  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.
authors.affiliation: Department of Thoracic Oncology, Lung Clinic Grosshansdorf GmbH, Airway Research Center North (ARCN), German Centre for Lung Research (DZL), Grosshansdorf, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
authors.affiliation: Comprehensive Medicine 1, Saitama Medical Center, Jichi Medical University, Saitama Prefecture, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hagiwara
authors.affiliation: Department of Respiratory Medicine, Shanghai Chest Hospital, Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Baohui
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Clinical Pharmacology and Chemotherapy, Russian Cancer Research Center, Moscow, Russian Federation.
authors.forename: Sergei
authors.initials: S
authors.lastname: Tjulandin
authors.affiliation: Pulmonary Clinic, Evangelical Lung Clinic, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Grohé
authors.affiliation: Department of Thoracic Oncology, Kansai Medical University Hirakata Hospital, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokoi
authors.affiliation: Thoracic Oncology Unit, National Cancer Institute "Pascale Foundation," Institute of Hospitalization and Scientific Care (IRCCS), Naples, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Morabito
authors.affiliation: Thoracic Oncology Unit, Department of Oncology, University of Turin, Turin, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Novello
authors.affiliation: Oncology Department, Hospital of the Sea, Barcelona, Spain.
authors.forename: Edurne
authors.initials: E
authors.lastname: Arriola
authors.affiliation: Pneumology, Le Mans General Hospital, Le Mans, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Molinier
authors.affiliation: Personalised Healthcare and Biomarkers, AstraZeneca, Macclesfield, United Kingdom.
authors.forename: Rose
authors.initials: R
authors.lastname: McCormack
authors.affiliation: Personalised Healthcare and Biomarkers, AstraZeneca, Macclesfield, United Kingdom.
authors.forename: Marianne
authors.initials: M
authors.lastname: Ratcliffe
authors.affiliation: Cell Biology and Biotherapy Unit, National Cancer Institute "Pascale Foundation," Institute of Hospitalization and Scientific Care (IRCCS), Naples, Italy. Electronic address: nicnorm@yahoo.com.
authors.forename: Nicola
authors.initials: N
authors.lastname: Normanno
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics; D005060:Europe; D005260:Female; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D016896:Treatment Outcome
chemical_list: D066246:ErbB Receptors
keywords: EGFR mutation; NSCLC; Plasma; Real-world; ctDNA