Analysis of Acquired Resistance Mechanisms to Osimertinib in Patients With EGFR-Mutated Advanced Non-small Cell Lung Cancer From the AURA3 Trial

Authors

Juliann Chmielecki
Tony Mok
Yi-Long Wu
Ji-Youn Han
Myung-Ju Ahn
Suresh S Ramalingam
Thomas John
Isamu Okamoto
James Chih-Hsin Yang
Frances A Shepherd
Krishna C Bulusu
Gianluca Laus
Barbara Collins
J Carl Barrett
Ryan J Hartmaier
Vassiliki Papadimitrakopoulou

Publication Date

2-27-2023

Journal

Nature Communications

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%).

Keywords

Humans, Carcinoma, Non-Small-Cell Lung, ErbB Receptors, Lung Neoplasms, Mutation, Protein Kinase Inhibitors, Disease Progression, Cancer, Lung cancer, Targeted therapies

DOI

10.1038/s41467-023-35962-x

PMID

36849516

PMCID

PMC9971022

PubMedCentral® Posted Date

2-27-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes