• 1 Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
  • 2 Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan
  • 3 Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital, Bangkok, Thailand
  • 4 Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium
  • 5 Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan
  • 6 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; and National University Bundang Hospital, Seongnam, Republic of Korea
  • 7 Division of Respiratory Medicine, Department of Medicine, Faculty of Medicine, University of Malaya Medical Centre, Lembah Pantai, Kuala Lumpur, Malaysia
  • 8 Medical Oncology Section, Hospital Universitario Málaga Regional, Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain
  • 9 Department of Respiratory Medicine, Kanazawa University Hospital, Kanazawa, Japan
  • 10 Department of Oncology, Jilin Provincial Cancer Hospital, Changchun, China
  • 11 Department of Thoracic Oncology and Medicine, National Hospital Organization, Shikoku Cancer Centre, Ehime, Japan
  • 12 Division of Oncology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, South Korea
  • 13 National Cheng Kung University Hospital, Tainan, Taiwan
  • 14 Roche Molecular Systems, Pleasanton, California
  • 15 Global Medicines Development, AstraZeneca, Cambridge, United Kingdom
  • 16 Precision Medicine and Genomics, Innovative Medicines and Early Development, AstraZeneca, Boston, Massachusetts
  • 17 Precision Medicine and Genomics, Innovative Medicines and Early Development, AstraZeneca, Cambridge, United Kingdom
  • 18 Emory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia
Clin. Cancer Res., 2019 11 15;25(22):6644-6652.
PMID: 31439584 DOI: 10.1158/1078-0432.CCR-19-1126


PURPOSE: To assess the utility of the cobas EGFR Mutation Test, with tissue and plasma, for first-line osimertinib therapy for patients with EGFR-mutated (EGFRm; Ex19del and/or L858R) advanced or metastatic non-small cell lung cancer (NSCLC) from the FLAURA study (NCT02296125).

EXPERIMENTAL DESIGN: Tumor tissue EGFRm status was determined at screening using the central cobas tissue test or a local tissue test. Baseline circulating tumor (ct)DNA EGFRm status was retrospectively determined with the central cobas plasma test.

RESULTS: Of 994 patients screened, 556 were randomized (289 and 267 with central and local EGFR test results, respectively) and 438 failed screening. Of those randomized from local EGFR test results, 217 patients had available central test results; 211/217 (97%) were retrospectively confirmed EGFRm positive by central cobas tissue test. Using reference central cobas tissue test results, positive percent agreements with cobas plasma test results for Ex19del and L858R detection were 79% [95% confidence interval (CI), 74-84] and 68% (95% CI, 61-75), respectively. Progression-free survival (PFS) superiority with osimertinib over comparator EGFR-TKI remained consistent irrespective of randomization route (central/local EGFRm-positive tissue test). In both treatment arms, PFS was prolonged in plasma ctDNA EGFRm-negative (23.5 and 15.0 months) versus -positive patients (15.2 and 9.7 months).

CONCLUSIONS: Our results support utility of cobas tissue and plasma testing to aid selection of patients with EGFRm advanced NSCLC for first-line osimertinib treatment. Lack of EGFRm detection in plasma was associated with prolonged PFS versus patients plasma EGFRm positive, potentially due to patients having lower tumor burden.

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