For children with neuroblastoma in whom the disease has returned (relapsed) or is not responding to treatment (refractory), the prognosis is unfortunately still unfavorable. Over the past 20 years, various chemotherapy combinations have been used worldwide, but until now they have hardly been compared. An international collaboration of researchers therefore wanted to find out which of these chemotherapy combinations works best. And also which combination can best be used as a base to add new drugs to, in order to further improve treatment.
BEACON neuroblastoma study
The BEACON neuroblastoma study is the largest comparative study to date in children with relapsed neuroblastoma. The study involved 160 children and young adults from 10 different European countries. Their disease had either not responded to initial treatment (refractory) or had recurred (relapsed). All were treated with one of three different chemotherapy combinations (temozolomide-based). Some of them additionally received the drug bevacizumab.
Bevacizumab is not a chemotherapy, but a form of targeted therapy. It reduces the formation of blood vessels in tumors and thus inhibits tumor growth.
Addition of bevacizumab
In children who received another chemotherapy drug (irinotecan or topotecan) in addition to temozolomide, the disease seemed to be suppressed more often than in children who received only temozolomide. The additional chemotherapy did cause more side effects, such as diarrhea or reduced white blood cell count.
In the group that received bevacizumab in addition to chemotherapy, more children responded to treatment (26%) than in the group that received chemotherapy alone (18%). Addition of bevacizumab seemed to enhance the effect of the chemotherapy drug irinotecan. When treated with a combination of bevacizumab, irinotecan and temozolomide, after 1 year the disease had not progressed in two-thirds of the children. The side effects of this combination appeared to be well tolerated.
In a follow-on study, the researchers compared the combination of bevacizumab with irinotecan and temozolomide with a new chemo-immunotherapy combination, to which dinutuximab was also added. That study has now been completed and results will be available soon.
The BEACON neuroblastoma study was conducted by a partnership of the Innovative Therapies for Children with Cancer (ITCC) and the European Association for Neuroblastoma Research (SIOPEN). From the Maxima Center, dr. Natasha van Eijkelenburg, dr. Paco Bautista and prof. dr. Michel Zwaan were involved in the study.
The scientific publication can be found here: Moreno L, et al. Bevacizumab, Irinotecan, or Topotecan Added to Temozolomide for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON-Neuroblastoma Trial. J Clin Oncol. 2024 Jan 8:JCO2300458.