Apatinib in recurrent anaplastic meningioma: a retrospective case series and systematic literature review

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 #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.