Lack of efficacy of bevacizumab plus irinotecan in cases of pediatric recurrent ependymoma - a Pediatric Brain Tumor Consortium study

A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in cases of pediatric recurrent ependymoma (EPN) to estimate sustained objective response rate and progression-free survival (PFS). Eligible patients received 2 doses of single-agent BVZ intravenously (10 mg/kg) 2 weeks apart and then BVZ CPT-11 every 2 weeks until progressive disease, unacceptable toxicity, or a maximum of 2 years of therapy. Correlative studies included diffusion-weighted and T1 dynamic contrast enhanced permeability imaging and tumor immunohistochemistry for vascular endothelial growth factor (VEGF)A and B, hypoxia inducible factor2, VEGF receptor (R)2, and carbonic anhydrase (CA)9. Thirteen evaluable patients received a median of 3 courses (range, 212) of BVZ CPT-11. No sustained response was observed in any patient. Median time to progression in 10 patients was 2.2 months (range, 1.96.3). Two patients had stable disease for 10 months and 12 months, respectively. Six-month PFS was 25.7 (SE 11.1). Grades IIII toxicities related to BVZ treatment included fatigue in 4 patients, systemic hypertension in 2, epistaxis in 1, headache in 1, and avascular necrosis of bone in 1. Although there was a decrease in the mean diffusion ratio following 2 doses of BVZ, it did not correlate with PFS. BVZ CPT-11 was well tolerated but had minimal efficacy in cases of recurrent EPN.