Department of Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Hangzhou, China.
Int J Cancer. 2021 Sep 1;149(5):1121-1128. doi: 10.1002/ijc.33677. Epub 2021 May 24.
Brain metastases (BMs) cause morbidity and mortality in patients with non-small cell lung cancer (NSCLC). The optimal management of epidermal growth factor receptor (EGFR)-mutated NSCLC with BM is debatable. We aimed to investigate the impact of different treatments among patients with EGFR-mutated NSCLC. A cohort of 2058 lung cancer patients with BM between 2013 and 2018 was retrospectively studied. A total of 571 patients with EGFR-mutated NSCLC and BM were enrolled. All patients had received EGFR tyrosine kinase inhibitors (TKIs). Overall survival (OS) was measured from the diagnosis of BM to death or last follow-up. With a median follow-up of 35.2 months (95% confidence interval [CI], 31.8-38.6), the median survival after BM was 21.3 months (95% CI, 19.0-23.6). Osimertinib resulted in significantly superior survival after resistance to front-line TKIs (P < 0.0035); the median OS reached 28.0 months (95% CI, 23.0-32.9), and the T790M status showed no difference in clinical effectiveness (P = 0.386). The combination of TKIs and chemotherapy/vascular endothelial growth factor (VEGF) inhibitors (anti-VEGF) tended to have longer OS (P = 0.271). Intracranial local radiotherapy significantly improved survival (P = 0.0008). In multivariable analysis, we noted that age, Karnofsky performance score, EGFR mutation type, number of BMs and the presence of extracranial metastasis were independent pretreatment prognostic factors. In conclusion, EGFR TKIs have a significant effect on patients with EGFR-mutant BM, and the application of osimertinib further improves survival outcomes regardless of T790M status. Patients who undergo intracranial local therapy can achieve a survival benefit.
脑转移（BMs）会导致非小细胞肺癌（NSCLC）患者的发病率和死亡率。表皮生长因子受体（EGFR）突变型 NSCLC 伴 BM 的最佳治疗方法仍存在争议。我们旨在探讨 EGFR 突变型 NSCLC 患者不同治疗方法的影响。回顾性研究了 2013 年至 2018 年间 2058 例伴 BM 的肺癌患者。共纳入 571 例 EGFR 突变型 NSCLC 伴 BM 的患者。所有患者均接受了 EGFR 酪氨酸激酶抑制剂（TKIs）治疗。从 BM 诊断到死亡或最后一次随访测量总生存期（OS）。中位随访 35.2 个月（95%置信区间[CI]，31.8-38.6），BM 后中位生存时间为 21.3 个月（95%CI，19.0-23.6）。奥希替尼在一线 TKI 耐药后显著提高了生存获益（P<0.0035）；中位 OS 达到 28.0 个月（95%CI，23.0-32.9），T790M 状态对临床疗效无差异（P=0.386）。TKI 联合化疗/血管内皮生长因子（VEGF）抑制剂（抗 VEGF）治疗的 OS 更长（P=0.271）。颅内局部放疗显著提高了生存获益（P=0.0008）。多变量分析显示，年龄、卡氏功能状态评分、EGFR 突变类型、BM 数量和颅外转移的存在是独立的预处理预后因素。总之，EGFR TKI 对 EGFR 突变型 BM 患者有显著疗效，奥希替尼的应用进一步提高了生存结局，而与 T790M 状态无关。接受颅内局部治疗的患者可以获得生存获益。
