Peng Wenying, Pu Xingxiang, Jiang Meilin, Wang Jingyi, Li Jia, Li Kang, Xu Yan, Xu Fang, Chen Bolin, Wang Qianzhi, Cao Jun, Chen Yong, Wu Lin
The Second Department of Thoracic Oncology, Hunan Cancer Hospital / The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410000, PR China.
Department of Oncology, The Central Hospital of Shaoyang City, No. 36, Qianyuan Alley, Shaoyang, 422000, PR China.
Lung Cancer. 2021 Feb;152:66-70. doi: 10.1016/j.lungcan.2020.12.008. Epub 2020 Dec 9.
Dacomitinib is a potent, irreversible and pan-HER tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). Currently, evidence of its activity on brain metastasis is lacking.
NSCLC patients diagnosed at Hunan Cancer Hospital between July, 2019 and July, 2020 with enhanced MRI-detected brain metastasis prior to treatment and laboratory-confirmed EGFR mutations were reviewed. In total, 14 EGFR-mutant NSCLC patients with brain metastasis were treated with first-line dacomitinib. The first radiographic review of chest CT and brain MRI was after one month and thereafter every 2 months. The objective response rate (ORR) and the depth of the brain metastasis response were determined via RECIST 1.1 and RANO-LM criteria.
In total, 14 of 59 EGFR-mutant advanced NSCLC patients who received first-line dacomitinib therapy had brain metastasis before treatment. Among these patients, 5 were given a dacomitinib starting dose of 45 mg once daily, while 9 received 30 mg daily until disease progression or unbearable toxicity. Eight patients harbored EGFR 19del, 5 had EGFR L858R, and one patient had EGFR G719A and I706 T co-mutations. The median duration of follow-up was 4.5 months. All patients received at least one review. The ORR was 92.9 % (13/14) and the disease control rate (DCR) was 100 %. A measurable response of the intracranial metastases was observed in 12 of 14 patients (85.7 %), including 12 of 13 (92.3 %) with brain parenchymal metastasis, but the one patient with meningeal metastasis did not respond well. All patients (100 %) had grade 1-2 adverse effects, but none discontinued treatment or required a dosage adjustment.
This case series study of 14 patients has shown that dacomitinib has potent efficacy for central nervous system (CNS) metastasis in EGFR-positive NSCLC. More data are required to confirm its advantages and optimize its clinical application.
达可替尼是一种强效、不可逆的泛表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI），用于治疗EGFR突变的非小细胞肺癌（NSCLC）。目前，缺乏其对脑转移活性的证据。
回顾性分析2019年7月至2020年7月在湖南省肿瘤医院确诊的NSCLC患者，这些患者在治疗前经增强MRI检测到脑转移且实验室确诊为EGFR突变。共有14例EGFR突变的NSCLC脑转移患者接受了一线达可替尼治疗。首次胸部CT和脑MRI影像学评估在1个月后进行，之后每2个月进行一次。通过RECIST 1.1和RANO-LM标准确定客观缓解率（ORR）和脑转移缓解深度。
在59例接受一线达可替尼治疗的EGFR突变晚期NSCLC患者中，共有14例在治疗前有脑转移。其中，5例患者接受的达可替尼起始剂量为每日45mg，9例患者接受每日30mg，直至疾病进展或出现无法耐受的毒性。8例患者为EGFR 19del，5例为EGFR L858R，1例患者为EGFR G719A和I706T共突变。中位随访时间为4.5个月。所有患者至少接受了一次评估。ORR为92.9%（13/14），疾病控制率（DCR）为100%。14例患者中有12例（85.7%）颅内转移灶出现可测量的缓解，其中13例脑实质转移患者中有12例（92.3%）缓解，但1例脑膜转移患者缓解不佳。所有患者（100%）均出现1-2级不良反应，但无一例停药或需要调整剂量。
本对14例患者的病例系列研究表明，达可替尼对EGFR阳性NSCLC的中枢神经系统（CNS）转移具有强效疗效。需要更多数据来证实其优势并优化其临床应用。
