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NTRK1融合作为EGFR外显子19突变型非小细胞肺癌的一种获得性耐药机制:一例报告

NTRK1-fusion as an acquired resistance mechanism in EGFRex19 mutated NSCLC: a case report.

作者信息

Li Jielin, Shi Yunyun, Zheng Mengge, Yang Chenkang, Gao Hong, Li Xiaoling

机构信息

Department of Thoracic Internal Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, China.

Genetron Health (Beijing) Co. Ltd., Beijing, China.

出版信息

Front Pharmacol. 2025 Aug 6;16:1571777. doi: 10.3389/fphar.2025.1571777. eCollection 2025.

Abstract

INTRODUCTION

A 73-year-old Chinese woman with no smoking history was diagnosed with stage IV adenocarcinoma of the lung in August 2020, presenting with left chest pain and multiple lung lesions.

PATIENT CONCERNS

The patient experienced chest pain for 2 months before diagnosis. Initial CT scans revealed multiple lung nodules, enlarged lymph nodes, and pleural effusion.

DIAGNOSIS

The diagnosis was confirmed as advanced NSCLC the left upper lobe of the lung with specific genetic alterations, including EGFR 19del, EGFR amplification, and TPR-NTRK1 fusion, through molecular testing.

INTERVENTIONS

Prior treatments included the first-line therapy gefitinib (250 mg/day) administered from September 2020 to June 2021, targeting the EGFR 19del mutation, achieving a partial response (PR). The second-line therapy osimertinib (80 mg/day) was administered from July 2021 to January 2022, targeting EGFR 19del and T790M mutations, with a progression-free survival (PFS) of approximately 7 months. The third-line therapy almonertinib, another third-generation EGFR-TKI, was administered from January 2022 to March 2022, but the response was poor, leading to further progression. After identifying NTRK fusion and EGFR amplification, the patient was administered larotrectinib as third-line treatment. Prior treatments included targeted therapies and chemotherapy.

OUTCOMES

Despite multiple lines of targeted therapy, the patient experienced rapid disease progression at several points, highlighting the challenges in managing NSCLC with complex genetic alterations.

CONCLUSION

This case underscores the importance of ongoing molecular testing and the potential need for combination therapies in managing advanced NSCLC with resistance to multiple targeted treatments. The current treatment with camrelizumab combined with chemotherapy shows promise, but further monitoring is necessary.

摘要

引言

一名73岁无吸烟史的中国女性于2020年8月被诊断为IV期肺腺癌,表现为左胸痛和多发肺部病变。

患者关注的问题

患者在诊断前胸痛2个月。初始CT扫描显示多发肺结节、淋巴结肿大及胸腔积液。

诊断

通过分子检测确诊为左上肺晚期非小细胞肺癌(NSCLC),伴有特定基因改变,包括表皮生长因子受体(EGFR)19号外显子缺失、EGFR扩增及TPR-NTRK1融合。

干预措施

先前治疗包括2020年9月至2021年6月给予一线治疗吉非替尼(250毫克/天),针对EGFR 19号外显子缺失突变,获得部分缓解(PR)。2021年7月至2022年1月给予二线治疗奥希替尼(80毫克/天),针对EGFR 19号外显子缺失和T790M突变,无进展生存期(PFS)约7个月。2022年1月至2022年3月给予三线治疗阿美替尼,另一种第三代EGFR酪氨酸激酶抑制剂(EGFR-TKI),但反应不佳,导致疾病进一步进展。在确定NTRK融合和EGFR扩增后,患者接受拉罗替尼作为三线治疗。先前治疗包括靶向治疗和化疗。

结果

尽管进行了多线靶向治疗,患者在多个阶段疾病仍快速进展,凸显了管理具有复杂基因改变的NSCLC的挑战。

结论

该病例强调了持续分子检测的重要性以及在管理对多种靶向治疗耐药的晚期NSCLC中联合治疗的潜在需求。目前卡瑞利珠单抗联合化疗的治疗显示出前景,但仍需进一步监测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5095/12364927/cad6fa7170f1/fphar-16-1571777-g001.jpg

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