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大细胞神经内分泌癌中可操作的基因组改变:欧洲的一系列病例中,患者接受了小分子抑制剂的治疗

Frank W J Heijboer¹, Marta Brambilla², Mario Occhipinti²

¹Department of Respiratory Medicine, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands.

JCO precision oncology

|November 14, 2025

概括

大细胞神经内分泌癌 (LCNEC) 中可操作的基因组改变 (AGAs) 在50%的病例中对小分子抑制剂 (SMIs) 有反应. 然而,在LCNEC中AGA的分子测试仍未得到充分利用,因此需要标准化查.

科学领域:

在瘤学瘤学.
基因组学就是基因组学.
药理学药理学是指药理学的学科.

背景情况:

大细胞神经内分泌癌 (LCNEC) 是神经内分泌瘤的一个罕见亚型.
在LCNEC中,可操作的基因组改变 (AGAs) 很少被发现.
小分子抑制剂 (SMIs) 在LCNEC患有AGAS患者的疗效尚未得到充分证实.

研究的目的:

评估LCNEC患者的应答率和生存结果,这些患者携带AGA并接受SMI治疗.
评估分子检测和AGA检测在全国LCNEC患者队列中的频率.

主要方法:

一项欧洲多中心队列研究包括LCNEC患者 (≥18岁) 与AGA接受SMI治疗.
评估了整体存活率 (OS) 和放射性反应.
用荷兰癌症登记处 (NCR) 分析了第四阶段LCNEC (2016-2022) 的分子测试率和AGA类型.

主要成果:

确定了28名LCNEC患者的AGAs;常见的AGAs包括EGFR突变 (35.7%) 和ALK融合 (32.1%).
平均生存期为14.6个月;在38个SMI治疗线路中观察到50%的部分响应率.
在NCR中,53.7%的IV期LCNEC患者接受了分子检测,检测到22.3%的AGAs.

结论:

用SMI治疗的LCNEC和AGA患者实现了显著的响应率 (50%),包括持久的响应.
在LCNEC中对AGAs的分子测试仅在约一半的患者中进行.
在LCNEC中对AGAs进行标准化分子测试对于确定符合针对性治疗的患者至关重要.

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