Department of Neurosurgery, Shandong Cancer Hospital Affiliated to Shandong University; Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences , Jinan, China.
Department of Neurosurgery, The People's Hospital of Zhang Qiu Area , Jinan, China.
Cancer Biol Ther. 2020 Jul 2;21(7):583-589. doi: 10.1080/15384047.2020.1740053. Epub 2020 Mar 25.
Up to now, no proven effective medical therapy for surgery and radiation-refractory anaplastic meningioma (AM) exists. Patients with vascular endothelial growth factor receptor 2 (VEGFR-2) positive meningiomas showed significantly shorter progression-free survival. Apatinib is a small-molecule antiangiogenic agent that selectively inhibits VEGFR-2. We report three cases of recurrent AM (VEGFR-2 positive) treated with apatinib. After apatinib treatment, the best outcome for all three patients was the partial response. The Progression-free survival was 17.3 months, 10.3 months, and 14+ months, respectively. The third patient lost follow-up after the last review. The overall survival was 28.5 months and 18 months, respectively. The main adverse events were hypertension, hand-foot syndrome, and myelosuppression. Apatinib is active in recurrent AM patients and this is the first report in the world. It is promising to launch a Phase II clinical trial of apatinib to further evaluate its efficacy on AM.
Anaplastic meningioma (AM) are rare and aggressive tumors with high recurrence rates despite optimal surgical or medical management. Up to now, no proven effective medical therapy, surgery, or radiation-refractory for AM exist. The progression-free survival (PFS) of patients with vascular endothelial growth factor receptor 2 (VEGFR-2)-positive meningiomas was significantly low. Apatinib (YN968D1) is a small-molecule antiangiogenic agent that selectively inhibits VEGFR-2.
CASE #1: A 47-year-old Asian female patient with malignant meningioma underwent four operations and three radiotherapies. She was given a 500 mg apatinib daily oral treatment, and the dosage was halved to 250 mg 3 months into the treatment. According to the Response Assessment in Neuro-Oncology (RANO) evaluation criteria, the best outcome during treatment was the partial response (PR) 6 months after the treatment. The PFS was 17.3 months, whereas the overall survival (OS) was 28.5 months. The best change in the Karnofsky performance scale (KPS) was a 10-point increase. The main adverse events included anemia (grade II), thrombocytopenia (grade II), and proteinuria (grade I).
CASE #2: A 71-year-old Asian woman with AM underwent two operations and two gamma knife stereotactic radiotherapies. She was given a 500 mg apatinib daily oral treatment with a follow-up period of 18 months. apatinib was taken orally for 10 months. According to the RANO evaluation criteria, the best outcome during treatment was PR. The PFS was 10.3 months, whereas the OS was 18 months. The best change in KPS was a 20-point increase. The main adverse events included hypertension (grade II), hand-foot syndrome (grade II), and fecal ocular blood (grade II). Case #3: A 16-year-old Asian girl with AM underwent two operations and two radiotherapies. She was given a 250 mg apatinib daily oral treatment with a follow-up period of 16 months. Apatinib was taken orally for 8 months. The patient did not follow-up after the last review of the brain-enhanced magnetic resonance imaging. According to the RANO evaluation criteria, the best outcome during treatment was PR. The PFS was 14+ months, and the best change in KPS was a 10-point increase. The main adverse events included hypertension (grade I) and hand-foot syndrome (grade I).
Apatinib is actively used in treating patients with recurrent AM. A randomized trial and phase II clinical trial of this inhibitor should be performed to further evaluate its efficacy in treating malignant meningioma.
间变性脑膜瘤(AM)是一种罕见的侵袭性肿瘤,即使采用最佳的手术或药物治疗,其复发率仍很高。目前,对于手术和放疗抵抗的 AM 尚无有效的治疗方法。血管内皮生长因子受体 2(VEGFR-2)阳性脑膜瘤患者的无进展生存期(PFS)明显较低。阿帕替尼(YN968D1)是一种小分子抗血管生成药物,可选择性抑制 VEGFR-2。
病例 1:一名 47 岁亚裔女性,患有恶性脑膜瘤,曾接受过 4 次手术和 3 次放疗。她每天口服 500mg 阿帕替尼,治疗 3 个月后剂量减半至 250mg。根据神经肿瘤反应评估标准(RANO)评估,治疗期间的最佳疗效为部分缓解(PR),治疗 6 个月后。PFS 为 17.3 个月,OS 为 28.5 个月。卡氏功能状态量表(KPS)的最佳改善为增加 10 分。主要不良反应包括贫血(II 级)、血小板减少(II 级)和蛋白尿(I 级)。
病例 2:一名 71 岁亚裔女性,患有 AM,曾接受过 2 次手术和 2 次伽玛刀立体定向放疗。她每天口服 500mg 阿帕替尼,随访 18 个月。阿帕替尼治疗 10 个月。根据 RANO 评估标准,治疗期间的最佳疗效为 PR。PFS 为 10.3 个月,OS 为 18 个月。KPS 的最佳改善为增加 20 分。主要不良反应包括高血压(II 级)、手足综合征(II 级)和粪便潜血(II 级)。
病例 3:一名 16 岁亚裔女孩,患有 AM,曾接受过 2 次手术和 2 次放疗。她每天口服 250mg 阿帕替尼,随访 16 个月。阿帕替尼治疗 8 个月。患者在最后一次脑部增强磁共振成像复查后未随访。根据 RANO 评估标准,治疗期间的最佳疗效为 PR。PFS 为 14 个月以上,KPS 的最佳改善为增加 10 分。主要不良反应包括高血压(I 级)和手足综合征(I 级)。
阿帕替尼积极用于治疗复发性 AM 患者。应进行该抑制剂的随机试验和 II 期临床试验,以进一步评估其在治疗恶性脑膜瘤中的疗效。