ctDNA Determination of EGFR Mutation Status in European and Japanese Patients with Advanced NSCLC: The ASSESS Study

• Published in: Journal of thoracic oncology 2016-10, Vol.11 (10), p.1682-1689
• Main Authors: Reck, Martin, Hagiwara, Koichi, Han, Baohui, Tjulandin, Sergei, Grohé, Christian, Yokoi, Takashi, Morabito, Alessandro, Novello, Silvia, Arriola, Edurne, Molinier, Olivier, McCormack, Rose, Ratcliffe, Marianne, Normanno, Nicola
• Format: Article
• Language: English
• Subjects: Aged; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; ctDNA; EGFR mutation; Europe; Female; Humans; Japan; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Mutation; NSCLC; Plasma; Real-world; Receptor, Epidermal Growth Factor - genetics; Treatment Outcome
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1016/j.jtho.2016.05.036

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.