Genetic biomarker study of sunvozertinib for clinical prognosis and prediction in NSCLC with EGFR exon 20 insertion mutation.
Journal
Cell reports. Medicine
Journal Volume
6
Journal Issue
5
Start Page
Article number 102121
ISSN
2666-3791
Date Issued
2025-05-20
Author(s)
Xu, Yan
Zhao, Yanqiu
Doucet, Ludovic
Zhou, Jianying
Wang, Yongsheng
Planchard, David
Fan, Yun
Jin, Bo
Han, Zhigang
Greillier, Laurent
Mazieres, Julien
Sun, Meili
Hu, Ying
Song, Xia
Ding, Cuimin
Wu, Lin
Tang, Kejing
Liang, Li
Yao, Yu
Cheng, Ying
He, Yong
Ferreira, Bruna Pellini
Ghiringhelli, François
Felip, Enriqueta
Bosch-Barrera, Joaquim
Liu, Anwen
Yu, Yan
Dong, Xiaorong
Gao, Junzhen
Camidge, D Ross
Nian, Weiqi
Zhou, Chengzhi
Yang, Runxiang
John, Thomas
Gao, Bo
Bazhenova, Lyudmila
Nagasaka, Misako
Wang, Jianghong
Ren, Xiubao
Xu, Fei
Li, Wen
Zhao, Dahai
Wang, Huijie
Sun, Si
Huang, Jian'an
Zhu, Xuehua
Zheng, Li
Jänne, Pasi A
Wang, Mengzhao
Abstract
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.
Subjects
EGFR exon20ins
NSCLC
biomarker
sunvozertinib
SDGs
Type
journal article