Mu Yuxin, Yang Ke, Hao Xuezhi, Wang Yan, Wang Lin, Liu Yutao, Lin Lin, Li Junling, Xing Puyuan
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.
Front Oncol. 2020 Apr 28;10:603. doi: 10.3389/fonc.2020.00603. eCollection 2020.
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.
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。