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罕见的外显子18 G719A和外显子21 L833V复合表皮生长因子受体(EGFR)突变对第三代酪氨酸激酶抑制剂(TKI)伏美替尼显示出良好反应:一例报告及文献综述

Rare exon 18 G719A and exon 21 L833V compound EGFR mutations show favorable response to Third-Generation TKI Furmonertinib: A case report and literature review.

作者信息

Zhao Jijun, Wu Tao, Zhang Dongdong

机构信息

Department of Oncology, People's Hospital, Hubei University of Medicine, Xiangyang No. 1, Jiefang Road No.15, Xiangyang, Hubei, 441000, China.

Department of Oncology, the Second Affiliated Hospital of Dalian Medical University, No. 467, Zhongshan Road, Shahekou District, Dalian, 116001, China.

出版信息

Invest New Drugs. 2025 Apr;43(2):425-432. doi: 10.1007/s10637-025-01521-y. Epub 2025 Mar 27.

DOI:10.1007/s10637-025-01521-y
PMID:40146384
Abstract

EGFR exon 19 deletions and exon 21 point mutations are the most common mutations in lung adenocarcinoma, with patients deriving significant clinical benefits from EGFR tyrosine kinase inhibitors (TKIs). However, the efficacy of TKIs in rare compound EGFR mutations remains uncertain. We report a case of lung adenocarcinoma with concurrent EGFR exon 18 G719A and exon 21 L833V mutations, showing a favorable response to third-generation TKI treatment. We reported a case of a 63-year-old female patient with brain, bone, and adrenal metastases from lung adenocarcinoma. Next-generation sequencing analysis identified a rare EGFR exon 18 G719A mutation in combination with an EGFR exon 21 L833V mutation. The patient received furmonertinib as first-line treatment and achieved a sustained response lasting over 12 months. This is the first reported case highlighting the efficacy of a third-generation TKI in treating lung adenocarcinoma with this rare compound mutation. Our findings suggest that third-generation TKIs may be a viable therapeutic option for prolonging progression-free survival in this patient subset.

摘要

表皮生长因子受体(EGFR)第19外显子缺失和第21外显子点突变是肺腺癌中最常见的突变,患者可从EGFR酪氨酸激酶抑制剂(TKIs)中获得显著的临床益处。然而,TKIs对罕见的复合EGFR突变的疗效仍不确定。我们报告了一例同时发生EGFR第18外显子G719A和第21外显子L833V突变的肺腺癌病例,该病例对第三代TKI治疗表现出良好反应。我们报告了一例63岁女性肺腺癌脑、骨和肾上腺转移患者。二代测序分析发现了一种罕见的EGFR第18外显子G719A突变与EGFR第21外显子L833V突变的组合。该患者接受伏美替尼作为一线治疗,并获得了持续超过12个月的缓解。这是首次报道的突出第三代TKI治疗这种罕见复合突变肺腺癌疗效的病例。我们的研究结果表明,第三代TKIs可能是延长该患者亚组无进展生存期的可行治疗选择。

相似文献

1
Rare exon 18 G719A and exon 21 L833V compound EGFR mutations show favorable response to Third-Generation TKI Furmonertinib: A case report and literature review.罕见的外显子18 G719A和外显子21 L833V复合表皮生长因子受体(EGFR)突变对第三代酪氨酸激酶抑制剂(TKI)伏美替尼显示出良好反应:一例报告及文献综述
Invest New Drugs. 2025 Apr;43(2):425-432. doi: 10.1007/s10637-025-01521-y. Epub 2025 Mar 27.
2
The effectiveness of sequential afatinib and furmonertinib in an advanced lung adenocarcinoma with rare compound EGFR mutation (L833V/H835L).序贯使用阿法替尼和伏美替尼治疗罕见复合表皮生长因子受体(EGFR)突变(L833V/H835L)的晚期肺腺癌的疗效
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Medicine (Baltimore). 2023 Dec 29;102(52):e36667. doi: 10.1097/MD.0000000000036667.
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Effective treatment with icotinib in advanced lung adenocarcinoma harboring rare EGFR mutation G719A/L833V: A case report.伊可替尼治疗罕见 EGFR 突变 G719A/L833V 型晚期肺腺癌患者的疗效:一例报告。
Medicine (Baltimore). 2022 Aug 19;101(33):e30080. doi: 10.1097/MD.0000000000030080.
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[A Rare Case of Lung Adenocarcinoma with EGFR L833V/H835L Co-mutation 
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Clinical outcomes of EGFR-TKI treatment and genetic heterogeneity in lung adenocarcinoma patients with EGFR mutations on exons 19 and 21.表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)治疗的临床结果以及外显子19和21上存在EGFR突变的肺腺癌患者的基因异质性
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本文引用的文献

1
Non-Small Cell Lung Cancer, Version 4.2024, NCCN Clinical Practice Guidelines in Oncology.非小细胞肺癌临床实践指南(第 4.2024 版),NCCN 肿瘤学临床实践指南
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[A Rare Case of Lung Adenocarcinoma with EGFR L833V/H835L Co-mutation 
and Literature Review].[1例罕见的伴有EGFR L833V/H835L共突变的肺腺癌病例及文献复习]
Zhongguo Fei Ai Za Zhi. 2023 Oct 20;26(10):795-800. doi: 10.3779/j.issn.1009-3419.2023.102.36.
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EGFR p.V774M/p.L833V compound mutations in lung adenocarcinoma responded well to almonertinib: a case report.
肺腺癌中EGFR p.V774M/p.L833V复合突变对阿美替尼反应良好:一例报告
Front Oncol. 2023 May 12;13:1159308. doi: 10.3389/fonc.2023.1159308. eCollection 2023.
4
Complete response to first-line osimertinib monotherapy in a complex epidermal growth factor receptor mutant ( L833V / H835L ) lung adenocarcinoma patient: a case report.一线奥希替尼单药治疗复杂表皮生长因子受体突变(L833V/H835L)肺腺癌患者的完全缓解:一例报告。
Anticancer Drugs. 2023 Sep 1;34(8):939-941. doi: 10.1097/CAD.0000000000001523. Epub 2023 Apr 28.
5
Brief Report: EGFR L833V/H835L Duplex-Mutated NSCLC With Leptomeningeal Carcinomatosis Responsive to Osimertinib.简短报告:伴有柔脑膜癌病的EGFR L833V/H835L双突变非小细胞肺癌对奥希替尼有反应
Clin Lung Cancer. 2023 Jun;24(4):360-361. doi: 10.1016/j.cllc.2023.01.010. Epub 2023 Feb 9.
6
Afatinib treatment response in advanced lung adenocarcinomas harboring uncommon mutations.阿法替尼治疗罕见突变型晚期肺腺癌的疗效。
Thorac Cancer. 2021 Nov;12(21):2924-2932. doi: 10.1111/1759-7714.14156. Epub 2021 Sep 21.
7
The Predictive Values of Advanced Non-Small Cell Lung Cancer Patients Harboring Uncommon Mutations-The Mutation Patterns, Use of Different Generations of -TKIs, and Concurrent Genetic Alterations.具有罕见突变的晚期非小细胞肺癌患者的预测价值——突变模式、不同代-TKIs的使用及并发基因改变
Front Oncol. 2021 Aug 26;11:646577. doi: 10.3389/fonc.2021.646577. eCollection 2021.
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Mutation Spectrum of From 21,324 Chinese Patients With Non-Small Cell Lung Cancer (NSCLC) Successfully Tested by Multiple Methods in a CAP-Accredited Laboratory.在中国合格评定国家认可委员会(CNAS)认可的实验室,采用多种方法成功检测的 21324 例中国非小细胞肺癌(NSCLC)患者的突变谱。
Pathol Oncol Res. 2021 Apr 7;27:602726. doi: 10.3389/pore.2021.602726. eCollection 2021.
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Crit Rev Oncol Hematol. 2021 Jan;157:103194. doi: 10.1016/j.critrevonc.2020.103194. Epub 2020 Dec 11.
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Great Efficacy of Afatinib in a Patient with Lung Adenocarcinoma Harboring EGFR L833V/H835L Mutations: A Case Report.阿法替尼对携带EGFR L833V/H835L突变的肺腺癌患者具有显著疗效:一例病例报告
Onco Targets Ther. 2020 Oct 20;13:10689-10692. doi: 10.2147/OTT.S260157. eCollection 2020.