BRAF非V600E突变型肺癌靶向治疗的策略探索

Strategic Exploration of Targeted Therapy for BRAF Non-V600E Mutant Lung Cancer

背景与目的达拉非尼+曲美替尼/达拉非尼靶向治疗已被批准用于V-RAF小鼠肉瘤病毒癌基因同源B1(V-RAF murine sarcoma viral oncogene homolog B1, BRAF)发生第600位密码子上缬氨酸的氨基酸替代(amino acid substitution for valine at position 600, V600E)的肺癌患者,针对携带BF非V600E突变的肺癌患者的靶向治疗策略尚未确定。本研究拟探讨BF非V600E突变型肺癌靶向治疗的疗效,为临床治疗提供参考。方法计算机检索Pub Med、Cochrane Library、Embase、Web of Science、Clinicaltrials.gov、CBM、CNKI、万方数据库。收集BRAF非V600E突变型肺癌靶向治疗相关文献,对纳入文献进行描述性分析。结果符合纳入标准的文献10篇,包括3篇队列研究和7篇个案报道。18例BRAF非V600E突变型肺癌患者对维莫非尼无效;1例应用维莫拉非尼后获得部分缓解(partial response,PR),5例患者对BF抑制剂无反应;9例患者在曲美替尼单药治疗后潜在临床获益率为34%;7例患者对达拉非尼联合曲美替尼在无进展生存期(progression-free survival, PFS)上均有不同程度的获益;1例患者对索拉非尼有效。结论目前BF非V600E突变靶向治疗仍无标准治疗规范,挑战在于BF基因的异质性突变,不同的突变类型对靶向治疗的反应不同,真实世界研究证据匮乏,有必要开展进一步的大样本高质量研究为临床治疗方案的选择提供参考。

Background and objective Dab rafenib+Trametinib/Dabrafenib targeted therapy has been approved for V-RAF murine sarcoma viral oncogene homolog B1 with amino acid substitution for valine at position 600(BRAF V600 E)in lung cancer patients,however,the targeted therapy strategy for lung cancer patients with BRAF non-V600 E mutations has not been determined yet.This study intends to explore the efficacy of targeted therapy for BRAF non-V600 E mutant lung cancer,and provide a reference for clinical treatment.Methods Computer search of PubMed,Cochrane Library,Embase,Web of Science,Clinicaltrials.gov,CBM,CNKI,Wanfang database.Collect the relevant literature relevant on the targeted therapy of BRAF non-V600 E mutant lung cancer,and conduct a descriptive analysis of the included literature.Results There were10 articles that met the inclusion criteria,including 3 cohort studies and 7 case reports.18 patients with BRAF non-V600 E mutant lung cancer were ineffective to vermurafenib;1 patient obtained partial response(PR) after applying vermurafenib,5 patients did not respond to BRAF inhibitors;9 patients showed a potential clinical benefit rate of 34% after monotherapy with trametinib;7 patients have different degrees of benefit from dabrafenib and trametinib on progression-free survival(PFS);1 patient is effective to sorafenib.Conclusion At present,there is no standard treatment specification for BRAF non-V600 E mutation targeted therapy.The challenge lies in the heterogeneous mutation of BRAF gene.Different mutation types respond differently to targeted therapy.In addtion,real-world research evidence is scarce,so it is necessary to carry out further largesample high-quality research to provide reference for clinical practice.