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非小细胞肺癌(NSCLC)中HER2突变的研究进展与未来展望,尤其在中国

Advances and Future Perspectives of HER2 Mutations in Non-Small Lung Cancer (NSCLC), Especially in China.

作者信息

Liu Chang, Li Tao, Cui Xiaoran, Lv Yahui, Liu Min, Zhou Xin, Yang Fan, Dong Yi, Li Ruixin, Zhang Fan, Zhang Tong, Hu Yi

机构信息

Senior Department of Oncology, The First Medical Center, Chinese PLA General Hospital, Beijing, China.

Chinese PLA Key Laboratory of Oncology, Key Laboratory for Tumor Targeting Therapy and Antibody Drugs, Ministry of Education, Beijing, China.

出版信息

Cancer Control. 2025 Jan-Dec;32:10732748251347572. doi: 10.1177/10732748251347572. Epub 2025 Jun 5.

Abstract

HER2-mutated non-small lung cancer (NSCLC) in China represents a substantial patient population characterized by an unfavorable prognosis. However, at present, the main clinical treatment options are relatively limited. HER2 mutations in Chinese NSCLC (2019-2024) demonstrated 3.8%-5.6% prevalence via NGS, exceeding global baselines, with superior detection vs PCR (4.5% vs 3.1%). In addition, more attention was paid to molecular analysis and the detection rate of HER2 genomic alterations in NSCLC patients in eastern and northern China compared to other parts of China, which might be related to regional economic differences and geographic differences in lung cancer epidemiology. The evolving therapeutic landscape has established new-generation TKIs (pyrotinib) and antibody-drug conjugates (ADCs) like trastuzumab deruxtecan (T-Dxd) as targeted strategies for HER2-mutant NSCLC. Despite late research initiation, China rapidly advanced from retrospective analyses to pioneering new drug trials. In general, the incidence of HER2-mutated NSCLC in the Chinese population seems to be higher than the world average, and there is a large number of missed HER2-mutated NSCLC patients in China. In this field, ADCs and novel TKIs are being developed and researched in spurts, and new drugs are moving from back-line therapy to front-line therapy, and from single-drug regimens to combination regimens.

摘要

中国的HER2突变型非小细胞肺癌(NSCLC)患者数量众多,预后不良。然而,目前主要的临床治疗选择相对有限。通过二代测序(NGS)检测发现,2019 - 2024年中国NSCLC患者中HER2突变的发生率为3.8% - 5.6%,超过全球基线水平,且检测效果优于聚合酶链反应(PCR)(4.5%对3.1%)。此外,与中国其他地区相比,中国东部和北部地区对NSCLC患者的分子分析及HER2基因改变检测率更为关注,这可能与地区经济差异及肺癌流行病学的地理差异有关。不断发展的治疗格局已确立了新一代酪氨酸激酶抑制剂(TKI,如吡咯替尼)和抗体药物偶联物(ADC,如曲妥珠单抗德鲁昔康,T-Dxd)作为HER2突变型NSCLC的靶向治疗策略。尽管研究起步较晚,但中国迅速从回顾性分析发展到开展新药试验。总体而言,中国人群中HER2突变型NSCLC的发病率似乎高于世界平均水平,且中国有大量HER2突变型NSCLC患者被漏诊。在该领域,ADC和新型TKI正在加速研发,新药正从二线治疗转向一线治疗,从单药治疗方案转向联合治疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6637/12144369/d7a84862fa21/10.1177_10732748251347572-fig1.jpg

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