Candidate mechanisms of acquired resistance to first-line osimertinib in EGFR-mutated advanced non-small cell lung cancer

Juliann Chmielecki, Jhanelle E. Gray (), Ying Cheng, Yuichiro Ohe, Fumio Imamura, Byoung Chul Cho, Meng-Chih Lin, Margarita Majem, Riyaz Shah, Yuri Rukazenkov, Alexander Todd, Aleksandra Markovets, J. Carl Barrett, Ryan J. Hartmaier and Suresh S. Ramalingam
Additional contact information
Juliann Chmielecki: AstraZeneca
Jhanelle E. Gray: H. Lee Moffitt Cancer Center & Research Institute
Ying Cheng: Jilin Provincial Cancer Hospital
Yuichiro Ohe: National Cancer Center Hospital
Fumio Imamura: Osaka International Cancer Institute
Byoung Chul Cho: Yonsei University College of Medicine
Meng-Chih Lin: Chang Gung University
Margarita Majem: Hospital de la Santa Creu i Sant Pau
Riyaz Shah: Maidstone and Tunbridge Wells NHS Trust
Yuri Rukazenkov: AstraZeneca
Alexander Todd: Oncology R&D, AstraZeneca
Aleksandra Markovets: AstraZeneca
J. Carl Barrett: AstraZeneca
Ryan J. Hartmaier: AstraZeneca
Suresh S. Ramalingam: Emory University

Nature Communications, 2023, vol. 14, issue 1, 1-9

Abstract: Abstract Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), potently and selectively inhibits EGFR-TKI-sensitizing and EGFR T790M resistance mutations. In the Phase III FLAURA study (NCT02296125), first-line osimertinib improved outcomes vs comparator EGFR-TKIs in EGFRm advanced non-small cell lung cancer. This analysis identifies acquired resistance mechanisms to first-line osimertinib. Next-generation sequencing assesses circulating-tumor DNA from paired plasma samples (baseline and disease progression/treatment discontinuation) in patients with baseline EGFRm. No EGFR T790M-mediated acquired resistance are observed; most frequent resistance mechanisms are MET amplification (n = 17; 16%) and EGFR C797S mutations (n = 7; 6%). Future research investigating non-genetic acquired resistance mechanisms is warranted.

Date: 2023
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-35961-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35961-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-35961-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().