Martin Reck1, Koichi Hagiwara2, Baohui Han3, Sergei Tjulandin4, Christian Grohé5, Takashi Yokoi6, Alessandro Morabito7, Silvia Novello8, Edurne Arriola9, Olivier Molinier10, Rose McCormack11, Marianne Ratcliffe11, Nicola Normanno12. 1. Department of Thoracic Oncology, Lung Clinic Grosshansdorf GmbH, Airway Research Center North (ARCN), German Centre for Lung Research (DZL), Grosshansdorf, Germany. 2. Comprehensive Medicine 1, Saitama Medical Center, Jichi Medical University, Saitama Prefecture, Japan. 3. Department of Respiratory Medicine, Shanghai Chest Hospital, Jiao Tong University, Shanghai, People's Republic of China. 4. Department of Clinical Pharmacology and Chemotherapy, Russian Cancer Research Center, Moscow, Russian Federation. 5. Pulmonary Clinic, Evangelical Lung Clinic, Berlin, Germany. 6. Department of Thoracic Oncology, Kansai Medical University Hirakata Hospital, Osaka, Japan. 7. Thoracic Oncology Unit, National Cancer Institute "Pascale Foundation," Institute of Hospitalization and Scientific Care (IRCCS), Naples, Italy. 8. Thoracic Oncology Unit, Department of Oncology, University of Turin, Turin, Italy. 9. Oncology Department, Hospital of the Sea, Barcelona, Spain. 10. Pneumology, Le Mans General Hospital, Le Mans, France. 11. Personalised Healthcare and Biomarkers, AstraZeneca, Macclesfield, United Kingdom. 12. Cell Biology and Biotherapy Unit, National Cancer Institute "Pascale Foundation," Institute of Hospitalization and Scientific Care (IRCCS), Naples, Italy. Electronic address: nicnorm@yahoo.com.
Abstract
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 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. 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.
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 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. 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.
Authors: Lee S Schwartzberg; Hidehito Horinouchi; David Chan; Sara Chernilo; Michaela L Tsai; Dolores Isla; Carles Escriu; John P Bennett; Kim Clark-Langone; Christer Svedman; Pascale Tomasini Journal: NPJ Precis Oncol Date: 2020-06-24
Authors: Jamal Zaini; Elisna Syahruddin; Muhammad Yunus; Sita Laksmi Andarini; Achmad Hudoyo; Najmiatul Masykura; Refniwita Yasril; Asep Ridwanuloh; Heriawaty Hidajat; Fariz Nurwidya; Sony Suharsono; Ahmad R H Utomo Journal: Cancer Rep (Hoboken) Date: 2019-02-03