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