在驱动基因阳性NSCLC中针对性治疗抵抗后,对二次BRAF变异的现实世界分析
DuJiang Liu1,2, KaiBo Ding1,2, KaiLai Yin2,3
1Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer(IBMC), Chinese Academy of Sciences, No.1 East Banshan Road, Gongshu District, Hangzhou, 310022, Zhejiang, China.
Scientific reports
|September 1, 2024
概括
二次BRAF变化导致非小细胞肺癌 (NSCLC) 耐铁激酶抑制剂 (TKIs) 的耐药性. 与化疗或持续单途径TKIs相比,联合向疗法或局部治疗原进展显著改善了生存率.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 二次BRAF变异是驱动基因阳性非小细胞肺癌 (NSCLC) 中对氨酸激酶抑制剂 (TKIs) 的已知耐药机制.
- 对于二次BRAF变异的NSCLC患者的最佳治疗策略尚不清楚,缺乏建立的共识.
- 了解临床和遗传特征对于在这种耐性NSCLC群体中指导治疗至关重要.
研究的目的:
- 为了研究NSCLC患者在TKI治疗期间发生二次BRAF变异的临床和遗传特征.
- 评估不同治疗策略对该患者队列生存结果的影响.
- 确定TKI耐性NSCLC的标准化疗之外的有效治疗方法.
主要方法:
- 在江癌症医院接受TCI治疗的27名晚期NSCLC患者的医疗记录的回顾性审查 (2016年5月 - 2023年12月).
- 评估临床和遗传特征,重点关注BRAF变化的时间和性质.
- 多变量加速失效时间 (AFT) 模型分析,以比较治疗组 (化疗,联合向治疗,局部治疗,向单一治疗) 的生存率.
主要成果:
- 二次BRAF变异出现于TKI启动后28个月的中位数.
- 与化疗相比,联合向疗法 (TKIs,BRAF/MEK抑制剂) 和局部治疗原进展显著改善了整体存活率 (OS) (p<0.001).
- 沿着原始信号通路持续的向单疗法与较短的生存期有关 (p=0.034) 并比化疗效果较差 (中位数生存期:36个月与45个月).
结论:
- 结合向治疗和局部治疗策略,为具有二次BRAF变异的TKI耐药NSCLC提供比传统化疗更好的生存益处.
- 由于疗效降低,应避免持续单途径向单疗法.
- 这些发现支持个性化治疗方法,以获得了耐药机制的NSCLC患者.
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