A prospective, multicenter, comprehensive genomic profile signature study in patients with EGFR-mutant advanced non-small cell lung cancer at the first-line treatment failure of osimertinib

作者：Yuankai Shi, Dongqing Lv, Weineng Feng, Chang Liu, Puyuan Xing, Yu Yan, Jun Yin, Xiubao Ren, Junqiang Zhang, Gaohua Han, Yongchang Zhang, Shundong Cang, Jun Chen, Enguo Chen, Lingxin Meng, Yong Zhang · 发表于：Signal Transduction and Targeted Therapy · 年份：2025 · DOI：10.1038/s41392-025-02481-8 · 被引用次数：8 · 研究领域：Lung Cancer Treatments and Mutations、Cancer Genomics and Diagnostics、Colorectal Cancer Treatments and Studies

Osimertinib, the first approved third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), exhibits notable efficacy in EGFR-mutant non-small cell lung cancer (NSCLC). This is a prospective, multicenter, comprehensive genomic profile signature (GPS) study in paired tissue and plasma samples from 149 patients with advanced NSCLC harboring EGFR exon 19 deletion (Ex19del) or L858R mutation at the first-line treatment failure of osimertinib (NCT05219162). Next-generation sequencing (NGS) was used for comprehensive GPS analysis of paired tissue and plasma samples. Fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) were used for tissue samples, while droplet digital polymerase chain reaction (ddPCR) and NGS were used for plasma samples to perform a concordance analysis of MET amplification. At the first-line treatment failure of osimertinib (study entry), EGFR alterations in tissue samples included EGFR Ex19del (49.0%, 73/149), EGFR L858R mutation (43.0%, 64/149), EGFR amplification (32.9%, 49/149), EGFR L718Q/V mutation (4.7%, 7/149), and EGFR C797S mutation (3.4%, 5/149); bypass signaling activation and downstream pathway activation alterations included TP53 mutation (69.8%, 104/149) and MET amplification (30.9%, 46/149). Among the 136 patients with EGFR Ex19del/L858R mutation in tissue samples, 72.1% (98/136), 35.3% (48/136), and 32.4% (44/136) had TP53 mutations, EGFR amplification, and MET amplification, respectively. ...