Abstract:
Lung cancer harbouring BRAF mutations accounts for 4% of all non-small cell lung cancer (NSCLC) cases, identifying a relevant subset of patients that need to be promptly managed. Three subtypes of BRAF mutations have been described: class I (V600E), and class II and III (non-V600), with different prognostic and predictive outcomes. Pivotal phase II trials have demonstrated the efficacy of the double BRAF/MEK inhibition with dabrafenib plus trametinib in patients harbouring V600E mutations, making BRAF a mandatory requirement in the genetic portrait of advanced non-squamous lung cancer patients. However, non-V600 mutations represent around 50% of BRAF-mutant NSCLC patients, for which no specific targeted approaches are approved. A paradigm shift from the double BRAF/MEK inhibition to combinations with agents with distinct mechanisms of action, such as immune-checkpoint inhibitors, pan-RAF and selective ERK 1/2 inhibitors, is under investigation and may change the therapeutic landscape of BRAF-driven NSCLC. This paper provides a practical, concise and updated review on the therapeutic strategies in NSCLC with BRAF mutations.
摘要:
BRAF突变的肺癌占所有非小细胞肺癌(NSCLC)病例的4%。确定需要及时管理的相关患者子集。已经描述了BRAF突变的三种亚型:I类(V600E),以及II级和III级(非V600),具有不同的预后和预测结果。关键的II期试验已证明dabrafenib联合曲美替尼双重抑制BRAF/MEK对V600E突变患者的疗效,使BRAF成为晚期非鳞状细胞肺癌患者遗传肖像的强制性要求。然而,非V600突变代表约50%的BRAF突变NSCLC患者,没有批准具体的针对性方法。从双重BRAF/MEK抑制到与具有不同作用机制的药物组合的范式转变,比如免疫检查点抑制剂,pan-RAF和选择性ERK1/2抑制剂,正在调查中,可能会改变BRAF驱动的非小细胞肺癌的治疗前景。本文提供了一种实用的,关于BRAF突变的非小细胞肺癌治疗策略的简明和最新综述。