Ding Xi, Zhang Zengli, Jiang Tao, Li Xuefei, Zhao Chao, Su Bo, Zhou Caicun
Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
Department of Respiratory, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Cancer Med. 2017 Mar;6(3):555-562. doi: 10.1002/cam4.1014. Epub 2017 Jan 30.
BRAF mutation is one of the important driver oncogene in non-small-cell lung cancer (NSCLC). Data on Chinese patients with BRAF-mutant NSCLC are inadequate. Hence, we conducted this study to investigate the clinicopathologic features and outcomes of Chinese patients with NSCLC and BRAF mutations. We identified patients with BRAF-mutant NSCLC between January 2012 and April 2016. Patient characteristics and treatment outcomes were analyzed. In total, 1680 patients were included. Twenty-eight (1.7%) patients harbored BRAF mutations. Compared to patients with non-BRAF mutation, patients with BRAF mutations were associated with adenocarcinomas (89.3% vs. 70.6%, P = 0.048) and never smokers (78.6% vs. 56.7%, P = 0.019). There were no significant differences in the age, gender distribution, metastasis, or stage at first diagnosis between two groups. Response rates and progression-free survival (PFS) were similar between patient with BRAF mutations and EGFR (5.6 vs. 5.8 months; P = 0.277) or KRAS (5.6 vs. 4.7 months; P = 0.741) mutations to first-line chemotherapy. Compared to patients with non-V600E mutations, patients with V600E-mutated tumors had a shorter PFS to first-line chemotherapy, although this did not reach statistical significance (5.2 vs. 6.4 months; P = 0.561). In multivariate analyses, only ECOG PS remained the independent predictor of overall survival (HR = 0.208; P = 0.004). In conclusion, BRAF mutation in Chinese patients with NSCLC was rare. BRAF mutation is more likely to be associated with adenocarcinoma and never smokers. BRAF mutations are not associated with enhanced chemosensitivity and novel and effective drugs inhibiting the BRAF pathway are in urgent need.
BRAF 突变是非小细胞肺癌(NSCLC)中重要的驱动癌基因之一。关于中国 BRAF 突变型 NSCLC 患者的数据并不充分。因此,我们开展了这项研究,以调查中国 BRAF 突变型 NSCLC 患者的临床病理特征及预后情况。我们纳入了 2012 年 1 月至 2016 年 4 月期间的 BRAF 突变型 NSCLC 患者。分析了患者的特征及治疗结果。总共纳入了 1680 例患者。28 例(1.7%)患者存在 BRAF 突变。与非 BRAF 突变患者相比,BRAF 突变患者与腺癌相关(89.3% 对 70.6%,P = 0.048)且从不吸烟者更多(78.6% 对 56.7%,P = 0.019)。两组在年龄、性别分布、转移情况或初次诊断时的分期方面无显著差异。BRAF 突变患者与 EGFR 突变患者(5.6 个月对 5.8 个月;P = 0.277)或 KRAS 突变患者(5.6 个月对 4.7 个月;P = 0.741)一线化疗的缓解率及无进展生存期(PFS)相似。与非 V600E 突变患者相比,V600E 突变肿瘤患者一线化疗的 PFS 较短,尽管未达到统计学显著性(5.2 个月对 6.4 个月;P = 0.561)。在多因素分析中,仅 ECOG 体能状态仍是总生存期的独立预测因素(HR = 0.208;P = 0.004)。总之,中国 NSCLC 患者中 BRAF 突变罕见。BRAF 突变更可能与腺癌及从不吸烟者相关。BRAF 突变与化疗敏感性增强无关,迫切需要新型有效的 BRAF 通路抑制剂。