134O_PR - Plasma ctDNA analysis for detection of EGFR T790M mutation in patients (pts) with EGFR mutation-positive advanced non-small cell lung cancer (aNSCLC)

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session NSCLC targeted therapy and circulating biomarkers
Topics Translational Research
Non-Small Cell Lung Cancer
Basic Principles in the Management and Treatment (of cancer)
Presenter Suzanne Jenkins
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors S. Jenkins1, J.C. Yang2, S. Ramalingam3, K. Yu4, S. Patel5, S. Weston1, R. Lawrance6, M. Cantarini7, P. Jänne8, T. Mitsudomi9
  • 1Personalised Healthcare And Biomarkers, AstraZeneca, SK10 3JS - Macclesfield/GB
  • 2Department Of Oncology, National Taiwan University Hospital, 100 - Taipei/TW
  • 3Department Of Hematology And Medical Oncology, Winship Cancer Institute of Emory University, 30322 - Atlanta/US
  • 4Clinical Operations, Roche Molecular Systems, Inc., 94588 - Pleasanton/US
  • 5Oncology Companion Diagnostics Unit, Personalised Healthcare And Biomarkers, AstraZeneca, SG8 6HB - Royston/GB
  • 6Biometrics And Informatics, AstraZeneca, SK10 5TL - Macclesfield/GB
  • 7Global Medicines Development, AstraZeneca, SK10 4TG - Macclesfield/GB
  • 8Lowe Center For Thoracic Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 9Thoracic Surgery, Kinki University School of Medicine, 589-8511 - Osaka/JP



Osimertinib is an irreversible EGFR-TKI that targets the T790M EGFR-TKI resistance mutation as well as common EGFR-TKI-sensitive mutant forms of EGFR. Pt selection for two single-arm Phase II registration studies (AURA extension, NCT01802632; AURA2, NCT02094261) was based on detection of the T790M mutation using the cobas® EGFR Mutation Test for use with formalin-fixed, paraffin-embedded tissue (cobas tissue test). Plasma samples were collected from screened pts and analysed retrospectively using the cobas® EGFR Mutation Test v2.0 (cobas plasma test; plasma claims not yet available in the US). Next generation sequencing (NGS) analysis was also performed on these plasma samples.


Agreement (positive and negative) between the cobas tissue test and the cobas plasma test, for detection of EGFR mutations, was calculated in the pooled Phase II analysis set. Agreement between the cobas plasma test and NGS analysis of plasma was calculated using samples from AURA2 pts.


In the pooled analysis, the positive percentage agreement (PPA) and negative percentage agreement (NPA) between the cobas tissue test and plasma test were 61.4% and 78.6%, respectively for detection of T790M. In AURA2, the PPA and NPA between the cobas plasma test and NGS analysis of plasma were 91.5% and 91.1%, respectively. As of May 2015, comparable ORR was observed in the subset of pts with a positive T790M plasma test as for all patients selected using the cobas tissue test. Common sensitising mutations were also analysed. PPA and NPA between the cobas tissue test and plasma test were 75.6% and 98.1%, respectively, for the L858R mutation, and 85.1% and 98.0%, respectively, for exon 19 deletions.


Data indicate that approximately 60% of pts with T790M positive NSCLC, the biomarker against which treatment with osimertinib is targeted, could have avoided an invasive biopsy by use of a plasma test. However, for EGFR-TKI-resistant pts, without detectable T790M in plasma, a tissue-based test is advised to address the potential for false negative results from the plasma test. These results indicate the utility of both plasma- and tissue-based tests in the diagnostic setting.

Clinical trial identification

NCT01802632 and NCT02094261 (Release dates 25 February 2013 and 17 March 2014)

Legal entity responsible for the study





S. Jenkins, S. Patel, S. Weston, R. Lawrance, M. Cantarini: Employee and shareholder: AstraZeneca. J. Yang: Advisory boards: Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech, AstraZeneca, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis Oncology, Celgene. S. Ramalingam: Consultancy fees: AstraZeneca, Boehringer Ingelheim, Celgene, Genentech, Novartis, Lilly, Merck, Bristol-Myers Squibb. K. Yu: Employee: Roche Molecular Systems, Inc. P. Jänne: Consultancy fees: AstraZeneca, Pfizer, Roche Research support: AstraZeneca, Astellas Pharmaceuticals Stock ownership: Gatekeeper Pharmaceuticals Other: Post marketing royalties on DFCI owned patent on EGFR mutations licensed to Lab Corp. T. Mitsudomi: Advisory board: AstraZeneca, Boehringer-Ingelheim, Chugai, Pfizer Honoraria: AstraZeneca, Chugai, Boehringer-Ingelheim, Pfizer Research fund: Boehringer-Ingelheim, Chugai, Pfizer.