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
Journal Volume
14
Journal Issue
1
Date Issued
2023-12-01
Author(s)
Chmielecki, Juliann
Mok, Tony
Wu, Yi-Long
Han, Ji-Youn
Ahn, Myung-Ju
Ramalingam, Suresh S
John, Thomas
Okamoto, Isamu
Shepherd, Frances A
Bulusu, Krishna C
Laus, Gianluca
Collins, Barbara
Barrett, J Carl
Hartmaier, Ryan J
Papadimitrakopoulou, Vassiliki
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%).
SDGs
Type
journal article