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However, the impact of acquired EGFR amplification on the efficacy of third\u2010generation EGFR\u2010TKI against T790M remains uncertain. We aimed to investigate whether the presence of acquired EGFR amplification after first\u2010generation EGFR\u2010TKI resistance influences the efficacy of third\u2010generation EGFR\u2010TKI in patients with advanced non\u2010small\u2010cell lung cancer (NSCLC). We reviewed data from 275 advanced NSCLC patients harboring T790M after first\u2010generation EGFR\u2010TKI resistance. Patients were categorized into two groups based on the presence or absence of acquired EGFR amplification identified through next\u2010generation sequencing (NGS) after first\u2010line EGFR\u2010TKI treatment. We evaluated the efficacy of osimertinib used as a second\u2010line treatment. Among these patients, 59 exhibited acquired EGFR amplification, while 216 did not. The median progression\u2010free survival (PFS) was 12.20 months in the EGFR amplification group and 12.03 months in the non\u2010amplification group (<jats:italic>p<\/jats:italic>\u2009=\u20090.011), with median overall survival (OS) of 33.90 months and 23.30 months, respectively (<jats:italic>p<\/jats:italic>\u2009=\u20090.164). Multivariate analysis of PFS revealed that acquired EGFR amplification and EGFR 19del were independent prognostic factors for patients with T790M undergoing osimertinib. Additionally, subgroup analysis indicated a prolonged PFS in patients with EGFR 19del compared to those with EGFR 21L858R (<jats:italic>p<\/jats:italic>\u2009=\u20090.034) in the EGFR amplification group. Following first\u2010generation EGFR\u2010TKI resistance, advanced EGFR\u2010mutant NSCLC patients harboring both acquired T790M and EGFR amplification are likely to experience enhanced PFS with osimertinib. This phenomenon is particularly noteworthy among individuals with EGFR 19del.<\/jats:p>","DOI":"10.1111\/cas.16437","type":"journal-article","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T03:38:11Z","timestamp":1735702691000},"page":"753-763","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Osimertinib for <scp>EGFR<\/scp>\u2010Mutant <scp>NSCLC<\/scp> Patients With Acquired <scp>T790M<\/scp> and <scp>EGFR<\/scp> Amplification After First\u2010Generation <scp>EGFR<\/scp>\u2010<scp>TKI<\/scp> Resistance"],"prefix":"10.1111","volume":"116","author":[{"given":"Yidan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 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