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https://ahro.austin.org.au/austinjspui/handle/1/32281| 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. vpapadimitrakopoulou@gmail.com. |
Issue Date: | 27-Feb-2023 | Date: | 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 (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%). | URI: | https://ahro.austin.org.au/austinjspui/handle/1/32281 | DOI: | 10.1038/s41467-023-35962-x | ORCID: | 0000-0002-3611-0258 0000-0001-5033-0006 0000-0002-0757-3106 0000-0003-3399-5342 0000-0002-5092-6640 0000-0001-7416-6036 0000-0003-3172-1399 |
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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