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

Fiche publication

Date publication

avril 2025

Journal

Cell reports. Medicine

Auteurs

Membres identifiés du Cancéropôle Est :
Pr GHIRINGHELLI François

Tous les auteurs :
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

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/40334661

Résumé

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.