150P - EGFR mutations in circulating tumor DNA (ctDNA) and tissue rebiopsy at progression on treatment with EGFR tyrosine kinase inhibitors (TKI)

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Anticancer agents
Thoracic Malignancies
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Biological Therapy
Presenter Katja Mohorcic
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors K. Mohorcic1, I. Kern2, M. Rot3, T. Cufer4
  • 1Medical Oncology Unit, University Clinic Golnik, 4204 - Golnik/SI
  • 2Department Of Pathology, University Clinic Golnik, 4204 Glnik - Golnik/SI
  • 3Department Of Pathology, University Clinic Golnik, 4204 - Golnik/SI
  • 4Medical Oncology Unit, University Clinic Golnik, 4204 Golnik - Golnik/SI



CtDNA EGFR mutation (EGFRmu) analysis is used to improve detection of resistant mutations and to overcome the limitation of repeated tissue sampling after resistance to EGFR TKI develops. 50–60% of resistance mechanism is due to secondary EGFR T790M mutation. The aim of our analysis was to evaluate the type and frequency of EGFRmu in ctDNA and in tissue at disease progression on non-mutant specific EGFR TKI.


Since May 2014 ctDNA EGFRmu determination is a routine clinical practice at our hospital. 41 EGFRmu positive pts with advanced NSCLC were treated with non-mutant specific EGFR TKI since then and followed up at our clinic. Blood samples for EGFRmu analysis were taken at each scheduled visit. Tissue rebiopy was also performed at disease progression when feasible for the patient. Cobas EGFR Mutation Test v1 and v2 (Roche, USA) to detect 42 mutations in exons 18 to 21 at EGFR gene was used for tissue and plasma testing.


21/41 (51%) pts experienced radiological progression with or without clinical disease progression during the observation period. In 19/21 (90.5%) pts activating EGFRmu were detected in the blood at the time of progression (+/− 1 month), in addition in 9/21 (42.9%) pts T790M mutation was also detected. In 7 pts tissue rebiopsy was also performed at the time of progression. In 2 pts, where T790M mutation was already detected in ctDNA, it was also found in the tissue. Among 5 pts, where only activating mutations were present in the ctDNA at the time of progression, 3 pts also had T790M mutations confirmed in the tissue rebiopsy. Overall, T790M mutations in ctDNA and/or tissue was detected in 12/21 (57.6%) of all our pts at the time of progression.


We confirmed a high rate of ctDNA EGFRmu positivity at the time of progression on EGFR TKI in our group of routinely treated pts. The detection rate of T790M mutation was lower than expected – only 43%. However, tissue rebiopsy increased T790M mutation detection rate to 57.6%. Taking into account our limited results tissue rebiopsy is reasonable where it is feasible for the patient because further therapeutic options are available.

Clinical trial identification

Legal entity responsible for the study





All authors have declared no conflicts of interest.