Shetty Vijith, Babu Suresh
Department of Medical Oncology, K.S. Hegde Medical Academy, Mangalore, Karnataka, India.
Medical Oncologist, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India.
Indian J Cancer. 2019 Nov;56(Supplement):S31-S37. doi: 10.4103/ijc.IJC_455_19.
Central nervous system (CNS) metastases are a frequent and severe complication associated with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). The first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) have shown considerable efficacy in EGFR-mutated NSCLC. However, their limited potential to cross the blood-brain barrier (BBB) renders them less effective in the management of CNS metastases in NSCLC. Osimertinib, a third-generation irreversible EGFR-TKI with good potential to cross the BBB, has shown significant clinical activity and acceptable safety profile in patients with EGFR-positive NSCLC brain and leptomeningeal metastases. The progression-free survival (PFS) of up to 15.2 months in CNS metastases patients in the FLAURA trial and the CNS objective response rates (ORRs) of 54% and 43% in the AURA/AURA2 and BLOOM trials, respectively, have established the role of osimertinib in patients with NSCLC with CNS metastases. The AURA3 trial also reported a PFS of 8.5 months and overall ORR of 71%. These data have supported osimertinib to be recognized as a "preferred" first-line treatment for EGFR-positive metastatic NSCLC by the National Comprehensive Cancer Network (NCCN). With limited treatment options available, upfront administration of osimertinib in patients with NSCLC irrespective of EGFR T790M and CNS metastases may improve the overall response rate and potentially reduce the adverse effects of radiotherapy. Our review focuses on the management of EGFR-mutated NSCLC CNS metastases in the context of recent NCCN guidelines.
中枢神经系统（CNS）转移是与表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）相关的常见且严重的并发症。第一代和第二代EGFR酪氨酸激酶抑制剂（TKIs）在EGFR突变的NSCLC中已显示出相当大的疗效。然而，它们穿过血脑屏障（BBB）的潜力有限，使其在NSCLC中枢神经系统转移的管理中效果较差。奥希替尼是一种第三代不可逆EGFR-TKI，具有良好的穿过BBB的潜力，在EGFR阳性NSCLC脑转移和软脑膜转移患者中已显示出显著的临床活性和可接受的安全性。在FLAURA试验中，CNS转移患者的无进展生存期（PFS）长达15.2个月，在AURA/AURA2和BLOOM试验中，CNS客观缓解率（ORR）分别为54%和43%，这些结果确立了奥希替尼在NSCLC脑转移患者中的作用。AURA3试验还报告了PFS为8.5个月，总ORR为71%。这些数据支持奥希替尼被美国国立综合癌症网络（NCCN）认可为EGFR阳性转移性NSCLC的“首选”一线治疗药物。由于可用的治疗选择有限，无论EGFR T790M和CNS转移情况如何，在NSCLC患者中预先给予奥希替尼可能会提高总体缓解率，并有可能减少放疗的不良反应。我们的综述重点关注在最新NCCN指南背景下EGFR突变的NSCLC中枢神经系统转移的管理。
