ACTR-08. A PHASE II STUDY OF APATINIB PLUS TEMOZOLOMIDE IN ADULTS WITH REFRACTORY RECURRENT HIGH-GRADE GLIOMAS

There is no standard therapy for refractory recurrent high-grade gliomas. We assessed the efficacy and safety of apatinib, a new oral small-molecule tyrosine kinase inhibitor targeted vascular endothelial growth factor receptor 2, combined with temozolomide (TMZ) in patients with refractory recurrent high grade gliomas. METHOD: This was a single-arm phase prospective clinical trial. Thirty three patients with recurrent high-grade gliomas were enrolled from April 2016 to March 2018. They received oral apatinib (500mg qd) in combination with TMZ. TMZ was administrated at 200 mg/m2/d according to standard 5/28 days regimen for the patients who had not received TMZ before, and that patients who had experienced relapse from the standard 5/28 TMZ regimen, received continuous daily TMZ (50 mg/m2/d). After 12 cycles, the patients continued to take apatinib as maintenance until progression. The primary endpoint was a 6-month progression-free survival (PFS) rate. The 6-month PFS for glioblastoma (GBM) was 47.8% and 58.3% for anaplastic gliomas (AGs). The median PFS was 4.9 months for GBM and 6.3 months for AGs. The overall survival (OS) at 1 year was 36.2% for GBM and 17.9% for AGs. The median OS for GBM was 8.3 months and 10.6 months for AGs. The differences in PFS (P=0.77) or OS (P=0.70) between GBM and AGs did not reach significance. Five (25%) out of 20 patients with GBM demonstrated partial (3/20) or complete (2/20) radiographic response to treatment and 10/20 (50%) remained stable. Four (50%) out of 8 patients with AGs showed partial (3/8) or minor (1/8) response to treatment and 3/8 (37.5%) remained stable. The most common grade 3 to 4 nonhematologic toxicities were hypertension, hand-foot syndrome, proteinuria and elevated transaminase, which were acceptable. These data show that apatinib plus TMZ is effective and tolerable in patients with refractory recurrent high-grade gliomas.