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


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
27 02 2023
Historique:
received: 28 07 2021
accepted: 10 01 2023
entrez: 27 2 2023
pubmed: 28 2 2023
medline: 3 3 2023
Statut: epublish

Résumé

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%).

Identifiants

pubmed: 36849516
doi: 10.1038/s41467-023-35962-x
pii: 10.1038/s41467-023-35962-x
pmc: PMC9971022
doi:

Substances chimiques

osimertinib 3C06JJ0Z2O
ErbB Receptors EC 2.7.10.1
Protein Kinase Inhibitors 0
EGFR protein, human EC 2.7.10.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1071

Subventions

Organisme : NCI NIH HHS
ID : P30 CA138292
Pays : United States

Informations de copyright

© 2023. The Author(s).

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Auteurs

Juliann Chmielecki (J)

Translational Medicine, Oncology R&D, AstraZeneca, Boston, MA, USA.

Tony Mok (T)

State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong, China.

Yi-Long Wu (YL)

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.

Ji-Youn Han (JY)

Center for Lung Cancer, National Cancer Center, Goyang, Republic of Korea.

Myung-Ju Ahn (MJ)

Section of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Suresh S Ramalingam (SS)

Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.

Thomas John (T)

Medical Oncology, Olivia Newton-John Cancer Research Institute, Austin Health, Melbourne, VIC, Australia.

Isamu Okamoto (I)

Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

James Chih-Hsin Yang (JC)

Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan.

Frances A Shepherd (FA)

Departments of Medical Oncology and Hematology, Princess Margaret Cancer Centre, and the University of Toronto, Toronto, ON, Canada.

Krishna C Bulusu (KC)

Translational Medicine, Oncology R&D, AstraZeneca, Cambridge, UK.

Gianluca Laus (G)

Translational Medicine, Oncology R&D, AstraZeneca, Cambridge, UK.
Clinical Development, Merus, Utrecht, The Netherlands.

Barbara Collins (B)

Biometrics and Information Sciences, AstraZeneca, Cambridge, UK.
Simbiotic Consulting Ltd, Glasgow, UK.

J Carl Barrett (JC)

Translational Medicine, Oncology R&D, AstraZeneca, Boston, MA, USA.

Ryan J Hartmaier (RJ)

Translational Medicine, Oncology R&D, AstraZeneca, Boston, MA, USA.

Vassiliki Papadimitrakopoulou (V)

Department of Thoracic/Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. vpapadimitrakopoulou@gmail.com.
Clinical Development, Pfizer Inc, Houston, TX, USA. vpapadimitrakopoulou@gmail.com.

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Classifications MeSH