Genetic biomarker study of sunvozertinib for clinical prognosis and prediction in NSCLC with EGFR exon 20 insertion mutation

作者：Yan Xu, James Chih‐Hsin Yang, Yanqiu Zhao, Ludovic Doucet, Jianying Zhou, Yongsheng Wang, David Planchard, Yun Fan, Bo Jin, Zhigang Han, Laurent Greillier, Julien Mazières, Meili Sun, Ying Hu, Xia Song, Cuimin Ding, Lin Wu, Kejing Tang, Li Liang, Yu Yao, Ying Cheng, Yong He, Bruna Pellini, François Ghiringhelli, Enriqueta Felip, Joaquim Bosch‐Barrera, Anwen Liu, Yan Yu, Xiaorong Dong, Junzhen Gao, D. Ross Camidge, Weiqi Nian, Chengzhi Zhou, Runxiang Yang, Thomas John, Bo Gao, Lyudmila Bazhenova, Misako Nagasaka, Jianghong Wang, Xiubao Ren, Fei Xu, Wen Li, Dahai Zhao, Huijie Wang, Si Sun, Jianan Huang, Xuehua Zhu, Li Zheng, Pasi A. Jänne, Mengzhao Wang · 发表于：Cell Reports Medicine · 年份：2025 · DOI：10.1016/j.xcrm.2025.102121 · 被引用次数：4 · 研究领域：Lung Cancer Treatments and Mutations、Cancer Genomics and Diagnostics、Colorectal Cancer Treatments and Studies

This is a report of biomarker analysis for sunvozertinib, a leading epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeting EGFR exon 20 insertion mutation (exon20ins) non-small cell lung cancer (NSCLC). There is a positive correlation between positive EGFR exon20ins in plasma circulating tumor DNA (ctDNA) and advanced disease. Shorter progression-free survival and lower objective response rate (45.8% vs. 68.0%) were observed in patients with positive EGFR exon20ins compared to those with negative status. Droplet digital PCR analysis showed that the EGFR exon20ins allele in ctDNA decreased over time in 85.7% of patients, with the earliest clearance occurred after 1 week of sunvozertinib treatment. Acquired EGFR C797S is identified as a potential on-target resistance mutation to sunvozertinib. Finally, efforts are undertaken to investigate therapeutic approaches that aim to overcome the putative acquired resistance to sunvozertinib.