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Title: Analysis of acquired resistance mechanisms to osimertinib in patients with EGFR-mutated advanced non-small cell lung cancer from the AURA3 trial.
Austin Authors: Chmielecki, Juliann;Mok, Tony;Wu, Yi-Long;Han, Ji-Youn;Ahn, Myung-Ju;Ramalingam, Suresh S;John, Thomas ;Okamoto, Isamu;Yang, James Chih-Hsin;Shepherd, Frances A;Bulusu, Krishna C;Laus, Gianluca;Collins, Barbara;Barrett, J Carl;Hartmaier, Ryan J;Papadimitrakopoulou, Vassiliki
Affiliation: Translational Medicine, Oncology R&D, AstraZeneca, Boston, MA, USA.
State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong, China.
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
Center for Lung Cancer, National Cancer Center, Goyang, Republic of Korea.
Section of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
Medical Oncology, Olivia Newton-John Cancer Research Institute, Austin Health, Melbourne, VIC, Australia.
Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan.
Departments of Medical Oncology and Hematology, Princess Margaret Cancer Centre, and the University of Toronto, Toronto, ON, Canada.
Translational Medicine, Oncology R&D, AstraZeneca, Cambridge, UK.
Biometrics and Information Sciences, AstraZeneca, Cambridge, UK.
Olivia Newton-John Cancer Research Institute
Translational Medicine, Oncology R&D, AstraZeneca, Boston, MA, USA.
Department of Thoracic/Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Issue Date: 27-Feb-2023 2023
Publication information: Nature Communications 2023; 14(1)
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 (nā€‰=ā€‰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%).
DOI: 10.1038/s41467-023-35962-x
ORCID: 0000-0002-3611-0258
Journal: Nature Communications
Start page: 1071
PubMed URL: 36849516
ISSN: 2041-1723
Type: Journal Article
Subjects: Carcinoma, Non-Small-Cell Lung/drug therapy
Carcinoma, Non-Small-Cell Lung/genetics
ErbB Receptors/genetics
Lung Neoplasms/drug therapy
Lung Neoplasms/genetics
Protein Kinase Inhibitors/pharmacology
Protein Kinase Inhibitors/therapeutic use
Appears in Collections:Journal articles

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