Phase II, Open Label Randomized, Multicenter Trial (HERBY) of Bevacizumab in Paediatric Patients with newly diagnosed high-grade glioma

Grill, J et al, 2018, Journal of Clinical Oncology

Link to abstract


This paper presents the results of the HERBY study – a Phase II, randomized multicentre trial adding bevacizumab to temozolomide and radiotherapy in pediatric patients with high-grade gliomas. This trial was spurred by the success of bevacizumab in adult HGG.


This was a multi-centre randomized trial comparing the two treatment regimes. The primary end-point was EFS (progression, recurrence, or death) as assessed by central radiology review blinded to the treatment that the patient received.

Results Summary

121 patients were enrolled. The EFS did not differ significantly between the two treatment groups (Radiotherapy and temozolomide 11.8 months, Radiotherapy and temozolomide plus bevacizumab 8.2 months, p = 0.13). 
In overall survival adding bevacizumab did not reduce the risk of death. Death occurred in 28 patients (50%) in the radiotherapy and temozolomide group and 33 patients (55%) radiotherapy and temozolomide plus bevacizumab group. 
Importantly there were more serious adverse events in the bevacizumab group compared to the radiotherapy and temozolomide group without bevacizumab.


The trial wasn't powered to detect an effect in genetically-defined subgroups such as in tumors with histone mutations.

Bottom Line

Adding bevacizumab to radiotherapy and temozolomide did not improve EFS in pediatric patients with high-grade glioma. This is disappointing and different from the experience in previously reported adult trials using bevacizumab in adult high-grade glioma. This highlights the biological difference between adult and pediatric gliomas and the importance of conducting paediatric specific studies.

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