Real-world utilization of EGFR TKIs and prognostic factors for survival in EGFR-mutated non-small cell lung cancer patients with brain metastases
Real-world utilization of EGFR TKIs and prognostic factors for survival in EGFR-mutated non-small cell lung cancer patients with brain metastases
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DOI：
10.1002/ijc.33677
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发表时间：
2021-05-24
影响因子：
6.4
通讯作者：
Fan, Yun
中科院分区：
文献类型：
--
作者：
Yu, Xiaoqing;Sheng, Jiamin;Fan, Yun
脑转移(BMS)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)突变的非小细胞肺癌合并骨髓的最佳治疗方案尚有争议。我们的目的是研究不同治疗方法对EGFR突变的非小细胞肺癌患者的影响。对2013年至2018年间2058例肺癌合并骨髓瘤患者进行了回顾性研究。共纳入571例EGFR突变的非小细胞肺癌和骨髓患者。所有患者均接受了EGFR酪氨酸激酶抑制剂(TKIs)治疗。从诊断BM到死亡或最后一次随访，测量总生存期(OS)。中位随访期35.2个月(95%可信区间31.8~38.6)，中位生存期21.3个月(95%可信区间19.0~23.6)。Osimertinib对一线TKI耐药后的存活率显著提高(P<；0.0035)，中位OS达28.0个月(95%可信区间23.0-32.9月)，T790M状态在临床疗效方面无差异(P=0.386)。TKIs联合化疗/血管内皮细胞生长因子抑制剂(抗血管内皮细胞生长因子抑制剂)往往具有更长的OS(P=0.271)。颅内局部放疗明显提高了患者的生存率(P=0.0008)。在多因素分析中，年龄、Karnofsky功能评分、EGFR突变类型、骨髓间充质干细胞数目和有无颅外转移是独立的治疗前预后因素。总之，EGFR TKIs对EGFR突变的BM患者有显著影响，无论T790M状态如何，奥西美替尼的应用都进一步改善了生存结果。接受颅内局部治疗的患者可以获得生存益处。
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.