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，其中主要包括人表皮生长因子受体 2 (HER2) 突变、间质-上皮转化 (MET) 改变、c-ros 癌基因 1 (ROS1) 重排、转染期间重排 (RET) 融合、v-raf 小鼠肉瘤病毒癌基因同源物 B1 (BRAF) 突变和神经营养性肌钙蛋白受体激酶 (NTRK) 融合。大约 10%-50% 携带罕见基因变异的 NSCLC 患者会发生脑转移 (BM)。最近出现的小分子酪氨酸激酶抑制剂和大分子抗体药物偶联物 (ADC) 为患有罕见驱动基因改变的 NSCLC 患者带来了显着的生存获益。尽管大多数靶向药物能够有效控制脑部病变，并且有报道称新型 ADC 可以实现颅内缓解，但 BM 仍然是一个主要的治疗挑战。本综述讨论了罕见遗传变异和 BM 的 NSCLC 治疗的最新进展，特别关注颅内疗效，并探讨了如何最好地治疗这些患者的未来前景。© 2024 UICC。

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.© 2024 UICC.