Abstract:
In patients with non-small cell lung cancer (NSCLC), oncogenic variants present in <5% of cases are considered rare, the predominant of which include human epidermal growth factor receptor 2 (HER2) mutations, mesenchymal-epithelial transition (MET) alterations, c-ros oncogene 1 (ROS1) rearrangements, rearrangement during transfection (RET) fusions, v-raf mouse sarcoma virus oncogene homolog B1 (BRAF) mutations, and neurotrophic troponin receptor kinase (NTRK) fusions. Brain metastases (BMs) occur in approximately 10%-50% of patients with NSCLC harboring rare genetic variants. The recent advent of small-molecule tyrosine kinase inhibitors and macromolecular antibody-drug conjugates (ADCs) has conferred marked survival benefits to patients with NSCLC harboring rare driver alterations. Despite effective brain lesion control for most targeted agents and promising reports of intracranial remission associated with novel ADCs, BM continues to be a major therapeutic challenge. This review discusses the recent advances in the treatment of NSCLC with rare genetic variants and BM, with a particular focus on intracranial efficacy, and explores future perspectives on how best to treat these patients.
摘要:
在非小细胞肺癌(NSCLC)患者中,<5%的病例中存在的致癌变异被认为是罕见的,其中主要包括人类表皮生长因子受体2(HER2)突变,间充质-上皮转化(MET)改变,c-ros癌基因1(ROS1)重排,转染(RET)融合过程中的重排,v-raf小鼠肉瘤病毒癌基因同源物B1(BRAF)突变,和神经营养肌钙蛋白受体激酶(NTRK)融合。脑转移(BMs)发生在大约10%-50%的具有罕见遗传变异的NSCLC患者中。最近小分子酪氨酸激酶抑制剂和大分子抗体-药物缀合物(ADC)的出现为具有罕见驱动改变的NSCLC患者赋予了显著的生存益处。尽管大多数靶向药物都能有效控制脑部病变,并且有希望报道与新型ADC相关的颅内缓解,BM仍然是一个主要的治疗挑战。本文综述了近年来罕见遗传变异和BM,特别关注颅内功效,并探讨如何最好地治疗这些患者的未来观点。