Phase II, open-label, randomized, multicenter trial (HERBY) of Bevacizumab in pediatric patients with newly diagnosed high-grade glioma

Grill, Jacques; Massimino, Maura; Bouffet, Eric; Azizi, Amedeo A.; McCowage, Geoffrey; Ca�ete, Adela; Saran, Frank; Le Deley, Marie-C�cile; Varlet, Pascale; Morgan, Paul S.; Jaspan, Tim; Jones, Chris; Giangaspero, Felice

Abstract

Purpose
Bevacizumab (BEV) is approved in more than 60 countries for use in adults with recurrent glioblastoma. We evaluated the addition of BEV to radiotherapy plus temozolomide (RT+TMZ) in pediatric patients with newly diagnosed high-grade glioma (HGG).
Methods
The randomized, parallel group, multicenter, open-label HERBY trial (ClinicalTrials.gov identifier: NCT01390948) enrolled patients age ≥ 3 years to ≤ 18 years with localized, centrally neuropathology-confirmed, nonbrainstem HGG. Eligible patients were randomly assigned to receive RT + TMZ (RT: 1.8 Gy, 5 days per week, and TMZ: 75 mg/m² per day for 6 weeks; 4-week treatment break; then up to 12 3 28-day cycles of TMZ [cycle 1: 150 mg/m² per day, days 1 to 5; cycles 2 to 12: 200 mg/m² per day, days 1 to 5]) with or without BEV (10 mg/kg every 2 weeks). The primary end point was event-free survival (EFS) as assessed by a central radiology review committee that was blinded to treatment. We report findings of EFS at 12 months after the enrollment of the last patient.
Results
One hundred twenty-one patients were enrolled (RT+TMZ [n = 59]; BEV plus RT+TMZ [n = 62]). Central radiology review committee–assessed median EFS did not differ significantly between treatment groups (RT+TMZ, 11.8 months; 95% CI, 7.9 to 16.4 months; BEV plus RT+TMZ, 8.2 months; 95% CI, 7.8 to 12.7 months; hazard ratio, 1.44; P = .13 [stratified log-rank test]). In the overall survival analysis, the addition of BEV did not reduce the risk of death (hazard ratio, 1.23; 95% CI, 0.72 to 2.09). More patients in the BEV plus RT+TMZ group versus the RT+TMZ group experienced one or more serious adverse events (n = 35 [58%] v n = 27 [48%]), and more patients who received BEV discontinued study treatment as a result of adverse events (n = 13 [22%] v n = 3 [5%]).
Conclusion
Adding BEV to RT+TMZ did not improve EFS in pediatric patients with newly diagnosed HGG. Our findings were not comparable to those of previous adult trials, which highlights the importance of performing pediatric-specific studies.

Citation

Grill, J., Massimino, M., Bouffet, E., Azizi, A. A., McCowage, G., Cañete, A., …Giangaspero, F. (2018). Phase II, open-label, randomized, multicenter trial (HERBY) of Bevacizumab in pediatric patients with newly diagnosed high-grade glioma. Journal of Clinical Oncology, 36(10), https://doi.org/10.1200/JCO.2017.76.0611

• Journal Article Type: Article
• Acceptance Date: Dec 6, 2016
• Online Publication Date: Feb 7, 2018
• Publication Date: Apr 1, 2018
• Deposit Date: Mar 23, 2018
• Publicly Available Date: Aug 8, 2018
• Journal: Journal of Clinical Oncology
• Print ISSN: 0732-183X
• Electronic ISSN: 1527-7755
• Publisher: American Society of Clinical Oncology
• Peer Reviewed: Peer Reviewed
• Volume: 36
• Issue: 10
• DOI: https://doi.org/10.1200/JCO.2017.76.0611
• Public URL: https://nottingham-repository.worktribe.com/output/922654
• Publisher URL: http://ascopubs.org/doi/10.1200/JCO.2017.76.0611
• Contract Date: Mar 23, 2018