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65例BRAF突变型非小细胞肺癌患者的临床特征及治疗结果

Clinical Characteristics and Treatment Outcomes of 65 Patients With BRAF-Mutated Non-small Cell Lung Cancer.

作者信息

Mu Yuxin, Yang Ke, Hao Xuezhi, Wang Yan, Wang Lin, Liu Yutao, Lin Lin, Li Junling, Xing Puyuan

机构信息

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Department of Medical Oncology, Cancer Hospital of HuanXing, Beijing, China.

出版信息

Front Oncol. 2020 Apr 28;10:603. doi: 10.3389/fonc.2020.00603. eCollection 2020.

Abstract

BRAF mutation is an oncogenic driver gene in non-small cell lung cancer (NSCLC) with low frequency. The data of patients with NSCLC harboring BRAF mutations is rare. We conducted a retrospective multicenter study in Chinese patients with NSCLC harboring BRAF mutations between Jan 2017 and Jul 2019. A total of 65 patients treated in 22 centers were included, 54 harbored BRAF-V600E mutation and 11 had non-V600E mutations, including K601E, G469S, G469V, G469A, G596R, G466R, and T599dup. Of 18 patients with early-stage disease at diagnosis and underwent a resection, the median disease-free survival (DFS) was 43.2, 18.7, and 10.1 months of stage I, II, and IIIA patients, respectively. In 46 patients with advanced-stage disease at data cutoff, disease control rate (DCR), and progression-free survival (PFS) of first-line anti-BRAF targeted therapy was superior than chemotherapy in patients harboring BRAF-V600E mutation (DCR, 100.0 vs. 70.0%, = 0.027; median PFS, 9.8 vs. 5.4 months, = 0.149). Of 30 V600E-mutated patients who received anti-BRAF therapy during the course of disease, median PFS of vemurafenib, dabrafenib, and dabrafenib plus trametinib was 7.8, 5.8, and 6.0 months, respectively ( = 0.970). Median PFS were similar between V600E and non-V600E patients (5.4 vs. 5.4 months, = 0.825) to first-line chemotherapy. Nine patients were treated with checkpoint inhibitors, with median PFS of 3.0 months. Our data demonstrated the clinical benefit of anti-BRAF targeted therapy in Chinese NSCLC patients harboring BRAF-V600E mutation. The value of immunotherapy and treatment selection among non-V600E population needs further study.

摘要

BRAF突变是一种在非小细胞肺癌(NSCLC)中低频存在的致癌驱动基因。携带BRAF突变的NSCLC患者的数据很少。我们对2017年1月至2019年7月期间携带BRAF突变的中国NSCLC患者进行了一项回顾性多中心研究。共纳入了22个中心治疗的65例患者,其中54例携带BRAF-V600E突变,11例为非V600E突变,包括K601E、G469S、G469V、G469A、G596R、G466R和T599dup。在18例诊断时为早期疾病并接受了手术切除的患者中,I期、II期和IIIA期患者的无病生存期(DFS)中位数分别为43.2个月、18.7个月和10.1个月。在数据截止时处于晚期疾病的46例患者中,携带BRAF-V600E突变的患者一线抗BRAF靶向治疗的疾病控制率(DCR)和无进展生存期(PFS)优于化疗(DCR,100.0%对70.0%,P = 0.027;中位PFS,9.8个月对5.4个月,P = 0.149)。在疾病过程中接受抗BRAF治疗的30例V600E突变患者中,维莫非尼、达拉非尼以及达拉非尼联合曲美替尼的中位PFS分别为7.8个月、5.8个月和6.0个月(P = 0.970)。V600E和非V600E患者接受一线化疗的中位PFS相似(5.4个月对5.4个月,P = 0.825)。9例患者接受了检查点抑制剂治疗,中位PFS为3.0个月。我们的数据证明了抗BRAF靶向治疗对携带BRAF-V600E突变的中国NSCLC患者具有临床益处。免疫治疗在非V600E人群中的价值以及治疗选择需要进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddf/7198730/1b4b063a1ce6/fonc-10-00603-g0001.jpg

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