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.

Background

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 presentation

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).

Conclusion

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.

中文翻译：

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阿帕替尼治疗复发性间变性脑膜瘤：回顾性病例系列和系统文献综述。

到目前为止，尚无经证实有效的外科手术和难治性间变性脑膜瘤 (AM) 的药物疗法。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显着缩短。阿帕替尼是一种小分子抗血管生成剂，可选择性抑制 VEGFR-2。我们报告了三例用阿帕替尼治疗的复发性 AM（VEGFR-2 阳性）病例。阿帕替尼治疗后，所有三名患者的最佳结果是部分反应。无进展生存期分别为 17.3 个月、10.3 个月和 14+ 个月。第三位患者在最后一次复查后失去了随访。总生存期分别为 28.5 个月和 18 个月。主要不良事件为高血压、手足综合征和骨髓抑制。阿帕替尼对复发性 AM 患者有效，这是世界上第一份报告。有望启动阿帕替尼的II期临床试验，进一步评估其对AM的疗效。

背景

间变性脑膜瘤 (AM) 是一种罕见的侵袭性肿瘤，尽管进行了最佳的手术或药物治疗，但复发率很高。到目前为止，尚无经证实有效的药物治疗、手术或抗辐射治疗 AM。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) 显着较低。Apatinib (YN968D1) 是一种小分子抗血管生成剂，可选择性抑制 VEGFR-2。

案例展示

情况1

一名患有恶性脑膜瘤的 47 岁亚洲女性患者接受了四次手术和三次放射治疗。她每天口服 500 毫克阿帕替尼，治疗后 3 个月剂量减半至 250 毫克。根据神经肿瘤学反应评估 (RANO) 评估标准，治疗期间的最佳结果是治疗后 6 个月的部分反应 (PR)。PFS 为 17.3 个月，而总生存期 (OS) 为 28.5 个月。Karnofsky 性能量表 (KPS) 的最佳变化是增加了 10 分。主要不良事件包括贫血（Ⅱ级）、血小板减少（Ⅱ级）和蛋白尿（Ⅰ级）。

案例#2

一名患有 AM 的 71 岁亚洲女性接受了两次手术和两次伽马刀立体定向放射治疗。她每天接受 500 毫克阿帕替尼的口服治疗，随访期为 18 个月。口服阿帕替尼 10 个月。根据RANO评估标准，治疗期间的最佳结果是PR。PFS 为 10.3 个月，而 OS 为 18 个月。KPS 的最佳变化是提高了 20 点。主要不良事件包括高血压（II 级）、手足综合征（II 级）和粪便眼血（II 级）。

案例#3：一名患有 AM 的 16 岁亚洲女孩接受了两次手术和两次放射治疗。她每天接受 250 毫克阿帕替尼的口服治疗，随访期为 16 个月。口服阿帕替尼 8 个月。在最后一次检查脑增强磁共振成像后，患者没有进行随访。根据RANO评估标准，治疗期间的最佳结果是PR。PFS是14+个月，KPS最好的变化是提高了10点。主要不良事件包括高血压（I 级）和手足综合征（I 级）。

结论

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，以进一步评估其治疗恶性脑膜瘤的疗效。