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

Xu, Y; Yang, JC; Zhao, Y; Doucet, L; Zhou, J; Wang, Y; Planchard, D; Fan, Y; Jin, B; Han, Z; Greillier, L; Mazieres, J; Sun, M; Hu, Y; Song, X; Ding, C; Wu, L; Tang, K; Liang, L; Yao, Y; Cheng, Y; He, Y; Ferreira, BP; Ghiringhelli, F; Felip, E; Bosch-Barrera, J; Liu, A; Yu, Y; Dong, X; Gao, J; Camidge, DR; Nian, W; Zhou, C; Yang, R; John, T; Gao, B; Bazhenova, L; Nagasaka, M; Wang, J; Ren, X; Xu, F; Li, W; Zhao, D; Wang, H; Sun, S; Huang, J; Zhu, X; Zheng, L; J&#228;nne, PA; Wang, M

Author(s): Xu, Y; Yang, JC; Zhao, Y; Doucet, L; Zhou, J; Wang, Y; Planchard, D; Fan, Y; Jin, B; Han, Z; Greillier, L; Mazieres, J; Sun, M; Hu, Y; Song, X; Ding, C; Wu, L; Tang, K; Liang, L; Yao, Y; Cheng, Y; He, Y; Ferreira, BP; Ghiringhelli, F; Felip, E; Bosch-Barrera, J; Liu, A; Yu, Y; Dong, X; Gao, J; Camidge, DR; Nian, W; Zhou, C; Yang, R; John, T; Gao, B; Bazhenova, L; Nagasaka, M; Wang, J; Ren, X; Xu, F; Li, W; Zhao, D; Wang, H; Sun, S; Huang, J; Zhu, X; Zheng, L; Jänne, PA; Wang, M;
Details: Publication Year 2025-05-20,Volume 6,Issue #5,Page 102121
Journal Title: Cell Reports Medicine
Publication Type: Research article
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.
Publisher: Elsevier
Keywords: Humans; *Carcinoma, Non-Small-Cell Lung/genetics/drug therapy/pathology; ErbB Receptors/genetics; *Lung Neoplasms/genetics/drug therapy; Exons/genetics; Female; Male; Prognosis; *Biomarkers, Tumor/genetics; Middle Aged; *Mutagenesis, Insertional/genetics; Protein Kinase Inhibitors/therapeutic use; Aged; Circulating Tumor DNA/blood/genetics; Drug Resistance, Neoplasm/genetics; EGFR exon20ins; Nsclc; biomarker; sunvozertinib
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1016/j.xcrm.2025.102121
Open Access at Publisher's Site: https://doi.org/10.1016/j.xcrm.2025.102121
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-07-17 07:59:05

Last Modified: 2025-07-17 07:59:16