针对携带EGFR外显子20插入突变的非小细胞肺癌患者，进行sunvozertinib用于临床预后及预测的遗传生物标志物研究。
Genetic biomarker study of sunvozertinib for clinical prognosis and prediction in NSCLC with EGFR exon 20 insertion mutation.
作者信息
Xu Yan, Yang James Chih-Hsin, 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
机构信息
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan.
出版信息
Cell Rep Med. 2025 May 20;6(5):102121. doi: 10.1016/j.xcrm.2025.102121. Epub 2025 May 6.
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.
这是一篇关于sunvozertinib的生物标志物分析报告。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），用于治疗EGFR外显子20插入突变（exon20ins）的非小细胞肺癌（NSCLC）。血浆循环肿瘤DNA（ctDNA）中EGFR exon20ins呈阳性与疾病进展之间存在正相关。与EGFR exon20ins阴性患者相比，EGFR exon20ins阳性患者的无进展生存期更短，客观缓解率更低（45.8%对68.0%）。液滴数字PCR分析显示，85.7%的患者ctDNA中的EGFR exon20ins等位基因随时间减少，最早在sunvozertinib治疗1周后清除。获得性EGFR C797S被确定为对sunvozertinib的一种潜在的靶向耐药突变。最后，开展了相关研究，以探索旨在克服对sunvozertinib假定获得性耐药的治疗方法。
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