Neuroblastoma is a very aggressive paediatric cancer that affects approximately 90 children each year in Spain and accounts for around 10% of childhood cancers. A high proportion of patients do not respond well to current treatments or experience relapse, resulting in very low survival rates and highlighting the need to develop new therapeutic strategies. With this aim, Dr. Lucas Moreno from Vall d’Hebron, together with researchers from the University of Birmingham, has led an international clinical trial demonstrating that combining chemotherapy with a type of immunotherapy leads to improved treatment responses in patients with the poorest prognosis. The results have been published in the Journal of Clinical Oncology.

In this study, the team investigated the combined treatment of chemotherapy with the antibody dinutuximab beta, one of the few drugs specifically designed for a childhood cancer and aimed at eliminating tumour cells. “BEACON is the largest international clinical trial conducted to date evaluating this treatment in patients with treatment-resistant or relapsed neuroblastoma”, explains Dr. Lucas Moreno, head of the Paediatric Oncology and Haematology Service at Vall d’Hebron University Hospital and head of the Childhood Cancer and Blood Disorders Research Group at the Vall d’Hebron Research Institute (VHIR).

65 patients aged between one and 18 years with relapsed or treatment-resistant neuroblastoma took part in the BEACON trial. Patients were recruited from 29 centres across seven European countries. Two groups were established: 22 patients initially received chemotherapy alone, while 43 patients received a combination of chemotherapy and dinutuximab beta. The trial was designed for each patient to undergo six treatment cycles. However, in 13 patients who initially received chemotherapy alone, dinutuximab beta was added after the first cycles failed to achieve a satisfactory response, ensuring the best possible treatment for all children.

Treatment response was assessed based on tumour size reduction. The combination of immunotherapy and chemotherapy achieved tumour reduction in 30.2% of cases, compared with 18.2% in patients treated with chemotherapy alone.

Progression-free survival was also analysed, defined as the period during which the patient survives without tumour growth or the appearance of new lesions. Among patients who received combined chemotherapy and immunotherapy, median progression-free survival was 11.1 months, compared with just 3.8 months in patients who did not receive immunotherapy. One year after enrolment in the study, 44% of patients receiving the combined therapy were alive with stable disease, compared with 27% of those treated with chemotherapy alone.

The study also assessed the safety of this therapeutic combination. Overall, the observed side effects were mild, including fever, allergic reactions, drowsiness and dizziness.

“We have observed that the use of combined therapy is able to improve clinical outcomes in patients with relapsed or refractory neuroblastoma and could therefore represent a new therapeutic strategy for these children”, says Dr. Moreno.

The BEACON trial: a major international study focused on neuroblastoma

BEACON is a project aimed at improving the treatment of children and adolescents with relapsed or treatment-resistant neuroblastoma. The study is the result of collaboration between 43 hospitals across Europe, involving the European Neuroblastoma Group of the International Society of Paediatric Oncology (SIOPEN) and the Innovative Therapies for Children with Cancer (ITCC) consortium. In Spain, the study includes participation from Vall d’Hebron, Hospital Infantil Universitario Niño Jesús, Hospital Universitario La Fe and Hospital de Cruces, where a total of 225 children and adolescents with neuroblastoma were recruited.

Previously, results from another study within the same project that evaluated the combination of chemotherapy with a different immunotherapy, bevacizumab, also showed promising results. The findings of the BEACON trial have enabled the launch of the new BEACON2 trial. “With BEACON2, we will compare the benefits of chemotherapy combined with bevacizumab or with dinutuximab beta, as well as the combination of both. This trial is a platform for evaluating new drugs and combinations in neuroblastoma, and additional combinations will be incorporated in the coming years”, highlights Dr. Moreno. “It is essential to continue research to identify new strategies that can be offered to these children and their families in order to improve survival in such an aggressive tumour that currently has very limited therapeutic options”, he adds.

In parallel, the BEACON-BIO study is also underway, using samples obtained from patients in the trial to identify genomic biomarkers and analyse liquid biopsy data, helping to explain individual differences in treatment response and to advance personalised medicine.