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Analysis of acquired resistance mechanisms to osimertinib in patients with EGFR-mutated advanced non-small cell lung cancer from the AURA3 trial

Author

Listed:
  • Juliann Chmielecki

    (Translational Medicine, Oncology R&D, AstraZeneca)

  • Tony Mok

    (Chinese University of Hong Kong)

  • Yi-Long Wu

    (Guangdong Provincial People’s Hospital & Guangdong Academy of Medical Sciences)

  • Ji-Youn Han

    (National Cancer Center)

  • Myung-Ju Ahn

    (Sungkyunkwan University School of Medicine)

  • Suresh S. Ramalingam

    (Emory University School of Medicine)

  • Thomas John

    (Medical Oncology, Olivia Newton-John Cancer Research Institute, Austin Health)

  • Isamu Okamoto

    (Kyushu University)

  • James Chih-Hsin Yang

    (National Taiwan University Cancer Center)

  • Frances A. Shepherd

    (Princess Margaret Cancer Centre, and the University of Toronto)

  • Krishna C. Bulusu

    (Translational Medicine, Oncology R&D, AstraZeneca)

  • Gianluca Laus

    (Translational Medicine, Oncology R&D, AstraZeneca
    Clinical Development, Merus)

  • Barbara Collins

    (Biometrics and Information Sciences, AstraZeneca
    Simbiotic Consulting Ltd)

  • J. Carl Barrett

    (Translational Medicine, Oncology R&D, AstraZeneca)

  • Ryan J. Hartmaier

    (Translational Medicine, Oncology R&D, AstraZeneca)

  • Vassiliki Papadimitrakopoulou

    (University of Texas M.D. Anderson Cancer Center
    Clinical Development, Pfizer Inc)

Abstract

Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), potently and selectively inhibits EGFR-TKI-sensitizing and EGFR T790M resistance mutations. This analysis evaluates acquired resistance mechanisms to second-line osimertinib (n = 78) in patients with EGFR T790M advanced non-small cell lung cancer (NSCLC) from AURA3 (NCT02151981), a randomized phase 3 study comparing osimertinib with chemotherapy. Plasma samples collected at baseline and disease progression/treatment discontinuation are analyzed using next-generation sequencing. Half (50%) of patients have undetectable plasma EGFR T790M at disease progression and/or treatment discontinuation. Fifteen patients (19%) have >1 resistance-related genomic alteration; MET amplification (14/78, 18%) and EGFR C797X mutation (14/78, 18%).

Suggested Citation

  • Juliann Chmielecki & Tony Mok & Yi-Long Wu & Ji-Youn Han & Myung-Ju Ahn & Suresh S. Ramalingam & Thomas John & Isamu Okamoto & James Chih-Hsin Yang & Frances A. Shepherd & Krishna C. Bulusu & Gianluca, 2023. "Analysis of acquired resistance mechanisms to osimertinib in patients with EGFR-mutated advanced non-small cell lung cancer from the AURA3 trial," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35962-x
    DOI: 10.1038/s41467-023-35962-x
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