Open-label, multicentre, randomised, phase II study of EpSSG and the ITCC evaluating the addition of bevacizumab to chemotherapy in childhood and adolescent patients with metastatic soft tissue sarcoma (the BERNIE study)

Open-label, multicentre, randomised, phase II study of EpSSG and the ITCC evaluating the addition of bevacizumab to chemotherapy in childhood and adolescent patients with metastatic soft tissue sarcoma (the BERNIE study)
This paper reported on the results of a European pediatric Soft tissue sarcoma Group (EpSSG) and the European Innovative Therapies for Children with Cancer (ITCC) consortium. It was a multi-center, randomized phase II study that evaluated the addition of bevacizumab to standard chemotherapy in children and adolescents with metastatic rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma (NRSTS).
Patients were randomized to receive standard induction chemotherapy ( IVADo/IVA) or standard chemotherapy plus bevacizumab (7.5mg/kg every 3 weeks), surgery and/or radiotherapy, followed by maintenance chemotherapy (low dose cyclophosphamide and vinorelbine) with bevacizumab added to the experimental arm at 5mg/kg every 2 weeks of each cycle. The primary objective was event free survival (EFS).
154 patients in the study. 80 with standard chemotherapy and 74 standard chemotherapy plus bevacizumab. Disease histologies were evenly matched in the two arms.
The addition of bevacizumab to the chemotherapy backbone used in metastatic soft tissue sarcoma appeared tolerable but the primary end-point of event free survival did not show statistically significant improvement.
The lack of statistical significance for the primary end point may reflect the fact that the sample size, although realistic for this rare tumor population, was inadequate to show a treatment effect.
While the addition of bevacizumab to standard chemotherapy for metastatic soft tissue sarcoma in children and adolescents was well tolerated the primary end-point of event free survival did not show statistically significant improvement.