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

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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Publication Details

Journal
Cell Reports Medicine
Published
2025-05-01
DOI
https://doi.org/10.1016/j.xcrm.2025.102121
Citations
4
Primary Topic
Lung Cancer Treatments and Mutations
Type
article
Field-Weighted Citation Impact
6.07
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article

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

Yong He, Yanqiu Zhao, Xia Song, Yu Yao et al.
4 citations
Cell Reports Medicine
Lung Cancer Treatments and Mutations
6.07
article

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

Yong He, Yanqiu Zhao, Xia Song, Yu Yao, Weiqi Nian, Joaquim Bosch‐Barrera, David Planchard, Chengzhi Zhou, Lyudmila Bazhenova, François Ghiringhelli, Ying Cheng, Pasi Antero Janne, James Chih‐Hsin Yang, Julien Mazières, Ludovic Doucet, Jianghong Wang, Dahai Zhao, Li Zheng, Misako Nagasaka, Xiaorong Dong, Laurent Greillier, Yan Xu, Anwen Liu, Ying Hu, Bruna Pellini, D. Ross Camidge, Lin Wu, Thomas John, Enriqueta Felip, Meili Sun, Wen Li, Yongsheng Wang, Xiubao Ren, Li Liang, Yan Yu, Jianan Huang, Yun Fan, Xuehua Zhu, Si Sun, Huijie Wang, Bo Jin, Zhigang Han, Mengzhao Wang, Runxiang Yang, Jianying Zhou, Bo Gao, Fei Xu, Cuimin Ding, Junzhen Gao, Kejing Tang
article en
4 citations

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.

Cell Reports MedicineVol. 6(5)
Hebei Medical University (CN), Nanchang University (CN), Army Medical University (CN), Xinjiang Medical University (CN), Harbin Medical University (CN), Sun Yat-sen University (CN), Chongqing University (CN), Capital Medical University (CN), Anhui Medical University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Peking University (CN), Sichuan University (CN), Universitat de Girona (ES), Université Paris-Saclay (FR), Catalan Institute for Water Research (ES), Peter MacCallum Cancer Centre (AU), Peking Union Medical College Hospital (CN), Institut Gustave Roussy (FR), Blacktown & Mount Druitt Hospital (AU), Tianjin Medical University Cancer Institute and Hospital (CN), Moffitt Cancer Center (US), Centre Hospitalier Universitaire de Toulouse (FR), University of California San Diego (US), Zhengzhou University (CN), Soochow University (CN), West China Hospital of Sichuan University (CN), Clínica Girona (ES), Fudan University Shanghai Cancer Center (CN), Centre Georges François Leclerc (FR), University of California, Irvine Medical Center (US), First Affiliated Hospital of Guangzhou Medical University (CN), Jilin Province Tumor Hospital (CN), Zhejiang Cancer Hospital (CN), Vall d'Hebron Institut de Recerca (ES), Shanxi Provincial Cancer Hospital (CN), Third Affiliated Hospital of Harbin Medical University (CN), Institut de Cancérologie de l'Ouest (FR), Fourth Hospital of Hebei Medical University (CN), Jinan Central Hospital (CN), Beijing Chest Hospital (CN), Second Affiliated Hospital of Nanchang University (CN), Hunan Cancer Hospital (CN), Dana-Farber Cancer Institute (US), First Affiliated Hospital of Xi'an Jiaotong University (CN), Hôpital Larrey (FR), The First Affiliated Hospital, Sun Yat-sen University (CN), Wuhan Union Hospital (CN), National Taiwan University Hospital (TW), University of Colorado Cancer Center (US), First Hospital of China Medical University (CN), Peking University Third Hospital (CN), Second Affiliated Hospital of Anhui Medical University (CN), First Affiliated Hospital of Soochow University (CN), Chongqing Cancer Hospital (CN), Second Affiliated Hospital of Zhejiang University (CN), Hôpital de la Timone (FR), Shandong First Medical University (CN), First Affiliated Hospital of Nanchang University (CN), First Affiliated Hospital Zhejiang University (CN), Vall d'Hebron Institute of Oncology (ES), Inner Mongolia Medical University (CN), China Medical University (CN), Guangzhou Medical University (CN), University of Colorado Denver (US)
Zero hunger
Openalex Percentile: Top 4%
Lung Cancer Treatments and Mutations
6.07
DOIOpen Access PDFOpenAlex
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