TY - JOUR
T1 - Analysis of acquired resistance mechanisms to osimertinib in patients with EGFR-mutated advanced non-small cell lung cancer from the AURA3 trial
AU - Chmielecki, Juliann
AU - Mok, Tony
AU - Wu, Yi Long
AU - Han, Ji Youn
AU - Ahn, Myung Ju
AU - Ramalingam, Suresh S.
AU - John, Thomas
AU - Okamoto, Isamu
AU - Yang, James Chih Hsin
AU - Shepherd, Frances A.
AU - Bulusu, Krishna C.
AU - Laus, Gianluca
AU - Collins, Barbara
AU - Barrett, J. Carl
AU - Hartmaier, Ryan J.
AU - Papadimitrakopoulou, Vassiliki
N1 - Funding Information:
Thanks to all the patients and their families. The authors would also like to thank Aleksandra Markovets for her significant contributions to the work. The study (NCT02151981) was funded by AstraZeneca (Cambridge, UK), the manufacturer of osimertinib. The sponsor, AstraZeneca, was involved in the study design and analysis. The authors would like to acknowledge Robert Harrison, Ph.D., of Ashfield MedComms, an Inizio Company, for medical writing support that was funded by AstraZeneca, Cambridge, UK, in accordance with Good Publications Practice (GPP) guidelines ( https://www.ismpp.org/gpp-2022 ).
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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%).
AB - 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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U2 - 10.1038/s41467-023-35962-x
DO - 10.1038/s41467-023-35962-x
M3 - Article
C2 - 36849516
AN - SCOPUS:85148968879
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1071
ER -
