In a phase II study reported in the Journal of Clinical Oncology, Grill et al found that the addition of bevacizumab (Avastin) to radiotherapy plus temozolomide (RT + TMZ) did not improve event-free survival in pediatric patients with newly diagnosed high-grade glioma.
In the international open-label study, 121 patients aged 3 to 18 years with localized nonbrainstem disease from 51 sites in 14 countries were randomized between October 2011 and February 2015 to receive RT + TMZ with (n = 62) or without (n = 59) bevacizumab 10 mg/kg every 2 weeks. RT + TMZ consisted of RT at 1.8 Gy 5 days per week and TMZ at 75 mg/m2 per day for 6 weeks followed by a 4 weeks off, then up to twelve 28-day cycles at 150 mg/m2 per day on days 1 to 5 in cycle 1 and 200 mg/m2 per day on days 1 to 5 in cycles 2 to 12. The primary endpoint was event-free survival on blinded central radiology review. Results are reported as of 12 months after the enrollment of the last patient.
Median event-free survival was 8.2 months in the bevacizumab group vs 11.8 months in the RT + TMZ group (hazard ratio [HR] = 1.44, P = .13). Overall survival data are immature; on interim analysis, the addition of bevacizumab did not reduce the risk of death (HR = 1.23, 95% confidence interval = 0.72–2.09). Overall survival at 1 year was 75% vs 68%.
Grade ≥ 3 adverse events occurred in 70% of patients in the bevacizumab group vs 68% of the control group. Serious adverse events occurred in 58% vs 48% of patients. Adverse events led to discontinuation of study treatment in 22% vs 5% of patients.
The investigators concluded, “Adding [bevacizumab] to RT + TMZ did not improve [event-free survival] in pediatric patients with newly diagnosed [high-grade glioma]. Our findings were not comparable to those of previous adult trials, which highlights the importance of performing pediatric-specific studies.”
The study was funded by F. Hoffmann-La Roche Ltd.
Jacques Grill, MD, PhD, of the Department of Pediatric and Adolescent Oncology, Institut Gustave-Roussy, is the corresponding author for the Journal of Clinical Oncology article.
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