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

IF 11.7 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-05-20 Epub Date: 2025-05-06 DOI:10.1016/j.xcrm.2025.102121

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 Mazieres, Meili Sun, Ying Hu, Xia Song, Cuimin Ding, Lin Wu, Kejing Tang, Li Liang, Yu Yao, Ying Cheng, Yong He, Bruna Pellini Ferreira, 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, Jian'an Huang, Xuehua Zhu, Li Zheng, Pasi A Jänne, Mengzhao Wang

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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.

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sunvozertinib对EGFR外显子20插入突变NSCLC临床预后和预测的遗传生物标志物研究。

sunvozertinib是一种主要的表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI），靶向EGFR外显子20插入突变（外显子20ins）非小细胞肺癌（NSCLC）。血浆循环肿瘤DNA （ctDNA）中EGFR外显子20蛋白阳性与疾病进展呈正相关。EGFR外显子20ins阳性患者的无进展生存期较短，客观缓解率较低（45.8% vs. 68.0%）。微滴数字PCR分析显示，85.7%的患者ctDNA中EGFR外显子20ins等位基因随着时间的推移而下降，最早的清除发生在sunvozertinib治疗1周后。获得性EGFR C797S被确定为对sunvozertinib的潜在靶向耐药突变。最后，正在努力研究旨在克服对sunvozertinib的推定获得性耐药的治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.