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

2023-02-27

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

Journal Article

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0000-0002-3611-0258

0000-0001-5033-0006

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0000-0002-0757-3106

0000-0003-3399-5342

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#PLACEHOLDER_PARENT_METADATA_VALUE#

0000-0002-5092-6640

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0000-0001-7416-6036

0000-0003-3172-1399

10.1038/s41467-023-35962-x

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%).

link

Nature Communications 2023; 14(1)

Nature Communications

2041-1723