Ma Jia, Bi Jianping, Tuo Xiulin, Pi Guoliang, Li Ying, Li Yanping, Zeng Fanyu, Gong Hongyun, Hu Desheng, Han Guang
Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Oncology, Jianghan Oilfield General Hospital, Qianjiang, China.
J Thorac Dis. 2022 Feb;14(2):455-463. doi: 10.21037/jtd-22-96.
Brain metastases (BMs) develop in 20-65% of non-small cell lung cancer (NSCLC) patients and are associated with a poor prognosis. Apatinib, a tyrosine kinase inhibitor (TKI) that selectively inhibits the vascular endothelial growth factor receptor 2, is safe and significantly prolongs the survival of chemotherapy-refractory gastric cancer patients. This retrospective study evaluated the safety and efficacy of apatinib combined with concurrent brain radiotherapy in NSCLC patients with BMs.
This trial enrolled patients with non-recurrent BM from histologically-confirmed NSCLC without any limits regarding the BM size/quantity. Eligibility criteria were patients 18-75 years old with measurable BM from histologically-confirmed NSCLC (including both newly-diagnosed and previously treated NSCLC) and expected survival time greater than 3 months. Oral apatinib (500 or 250 mg/day) was started within 1 week prior to commencing whole brain radiotherapy with simultaneous integrated boost (WBRT-SIB) and continued until one week after radiotherapy completion. In addition to toxicities, analyzed outcomes included intracranial overall response rate (iORR), intracranial disease control rate (iDCR), intracranial progression free survival (iPFS), and overall survival (OS).
From July 2016 to January 2020, 16 patients were enrolled in this retrospective study. After 3 months of brain radiotherapy, the iORR was 75%, the iDCR was 100%, and the brain edema index (EI) was significantly reduced compared to that before brain radiation therapy (4.2 1.9; P=0.02). The median iPFS was 16.5 months [95% confidence interval (CI): 15.1-37.4 months]. The median OS was 26 months (95% CI: 17.0-54.0 months). Most of the patients tolerated apatinib well, but 7 patients had side effects, most commonly grade 1 or 2. Only 2 patients experienced grade 3 adverse events (hypertension and oral mucositis), and no grade 4 or 5 toxicities were observed.
Apatinib combined with WBRT-SIB appears to be safe and effective in treating BMs in NSCLC patients.
脑转移瘤（BMs）在20% - 65%的非小细胞肺癌（NSCLC）患者中发生，且与预后不良相关。阿帕替尼是一种选择性抑制血管内皮生长因子受体2的酪氨酸激酶抑制剂（TKI），它安全且能显著延长化疗难治性胃癌患者的生存期。这项回顾性研究评估了阿帕替尼联合同期脑部放疗在伴有BMs的NSCLC患者中的安全性和疗效。
本试验纳入了经组织学确诊为NSCLC且脑转移瘤无复发的患者，对脑转移瘤的大小/数量没有任何限制。纳入标准为年龄在18 - 75岁、经组织学确诊为NSCLC（包括新诊断和既往接受过治疗的NSCLC）且有可测量的脑转移瘤、预期生存时间大于3个月的患者。在开始全脑放疗同步推量（WBRT - SIB）前1周内开始口服阿帕替尼（500或250 mg/天），并持续至放疗完成后1周。除毒性外，分析的结局指标包括颅内总缓解率（iORR）、颅内疾病控制率（iDCR）、颅内无进展生存期（iPFS）和总生存期（OS）。
2016年7月至2020年1月，16例患者纳入了这项回顾性研究。脑部放疗3个月后，颅内总缓解率为75%，颅内疾病控制率为100%，与脑部放疗前相比脑水肿指数（EI）显著降低（4.2±1.9；P = 0.02）。颅内无进展生存期的中位数为16.5个月[95%置信区间（CI）：15.1 - 37.4个月]。总生存期的中位数为26个月（95% CI：17.0 - 54.0个月）。大多数患者对阿帕替尼耐受性良好，但7例患者有副作用，最常见的为1级或2级。仅2例患者出现3级不良事件（高血压和口腔黏膜炎），未观察到4级或5级毒性反应。
阿帕替尼联合WBRT - SIB在治疗NSCLC患者的脑转移瘤方面似乎是安全有效的。
