• 1 Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address:
  • 2 Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Clinical Oncology Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China. Electronic address:
  • 3 Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address:
  • 4 Department of Shanghai Lung Cancer, Shanghai Chest Hospital, Shanghai, China. Electronic address:
  • 5 Division of Haematology-Oncology, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address:
  • 6 Siriraj Hospital, Bangkok, Thailand. Electronic address:
  • 7 Beijing Cancer Hospital, Beijing, China. Electronic address:
  • 8 Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address:
  • 9 F. Hoffmann-La Roche Ltd., Basel, Switzerland. Electronic address:
  • 10 OzBiostat Pty Ltd., Sydney, NSW, Australia. Electronic address:
  • 11 Pharmaceutical Development Oncology, Roche Products Ltd., Welwyn Garden City, UK. Electronic address:
  • 12 Roche Molecular Systems, Pleasanton, CA, USA. Electronic address:
  • 13 Roche Molecular Systems, Pleasanton, CA, USA. Electronic address:
  • 14 Roche Molecular Systems, Pleasanton, CA, USA. Electronic address:
  • 15 Genentech Inc., South San Francisco, CA, USA. Electronic address:
  • 16 CStone Pharmaceuticals (Suzhou) Co., Ltd., Shanghai, China. Electronic address:
  • 17 Roche Molecular Systems, Pleasanton, CA, USA. Electronic address:
  • 18 State Key Laboratory of South China, Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong, China. Electronic address:
Lung Cancer, 2018 12;126:1-8.
PMID: 30527172 DOI: 10.1016/j.lungcan.2018.10.004


OBJECTIVE: Patients with advanced non-small-cell lung cancer (NSCLC) with an adenocarcinoma component are recommended to undergo epidermal growth factor receptor (EGFR) mutation testing when being considered for EGFR targeted therapy. We conducted an exploratory analysis to inform the clinical utility of EGFR mutation testing in blood cell-free DNA using the cobas®EGFR Mutation Test v2.

MATERIALS AND METHODS: Two EGFR mutation tests, a tissue-based assay (cobas® v1) and a tissue- and blood-based assay (cobas® v2) were used to analyze matched biopsy and blood samples (897 paired samples) from three Asian studies of first-line erlotinib with similar intent-to-treat populations. ENSURE was a phase III comparison of erlotinib and gemcitabine/platinum, FASTACT-2 was a phase III study of gemcitabine/platinum plus erlotinib or placebo, and ASPIRATION was a single-arm phase II study of erlotinib. Agreement statistics were evaluated, based on sensitivity and specificity between the two assays in subgroups of patients with increasing tumor burden.

RESULTS: Patients with discordant EGFR (tissue+/plasma-) mutation status achieved longer progression-free and overall survival than those with concordant (tissue+/plasma+) mutation status. Tumor burden was significantly greater in patients with concordant versus discordant mutations. Pooled analyses of data from the three studies showed a sensitivity of 72.1% (95% confidence interval [CI] 67.8-76.1) and a specificity of 97.9% (95% CI 96.0-99.0) for blood-based testing; sensitivity was greatest in patients with larger baseline tumors.

CONCLUSIONS: Blood-based EGFR mutation testing demonstrated high specificity and good sensitivity, and offers a convenient and easily accessible diagnostic method to complement tissue-based tests. Patients with a discordant mutation status in plasma and tissue, had improved survival outcomes compared with those with a concordant mutation status, which may be due to their lower tumor burden. These data help to inform the clinical utility of this blood-based assay for the detection of EGFR mutations.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.