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

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 ad...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9971022/
https://www.ncbi.nlm.nih.gov/pubmed/36849516
http://dx.doi.org/10.1038/s41467-023-35962-x
Descripción
Sumario: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%).

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