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

• DOI: 10.1016/j.ejca.2017.06.015
• Publication Date: 2017-08-23T08:45:26Z
• Authors: Julia C. Chisholm; Johannes H.M. Merks; Michela Casanova; Gianni Bisogno; Daniel Orbach; Jean-Claude Gentet; Anne-Sophie Thoma...; Pascal Chastagner; Stephen Lowis; Milind Ronghe; Kieran McHugh; Rick R. van Rijn; Magalie Hilton; Jeanette Bachir; Sabine Fürst-Reck...; Birgit Geoerger; Odile Oberlin
• Keywords: Male; Adolescent; European paediatric Soft tissue sarcoma Study Group (EpSSG) and the European Innovative Therapies for Children with Cancer (ITCC) Consortium; 610; Infant; Angiogenesis Inhibitors; Sarcoma; Soft Tissue Neoplasms; Induction Chemotherapy; Disease-Free Survival; Maintenance Chemotherapy; 3. Good health; Bevacizumab; 03 medical and health sciences; 0302 clinical medicine; Child, Preschool; Antineoplastic Combined Chemotherapy Protocols; Humans; Female; Bevacizumab; Metastatic soft tissue sarcoma; NRSTS; Paediatrics; RMS; Adolescent; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Child; Child, Preschool; Disease-Free Survival; Female; Humans; Induction Chemotherapy; Infant; Maintenance Chemotherapy; Male; Sarcoma; Soft Tissue Neoplasms; Oncology; Cancer Research; Preschool; Child

We evaluated the role of bevacizumab as part of the multi-modality treatment of children and adolescents with metastatic rhabdomyosarcoma (RMS) or non-rhabdomyosarcoma soft tissue sarcoma (NRSTS).Eligible patients aged ≥6 months to <18 years were randomised to receive induction chemotherapy (four cycles of IVADo + five cycles of IVA, ±bevacizumab), surgery and/or radiotherapy, followed by maintenance chemotherapy (12 cycles of low-dose cyclophosphamide + vinorelbine, ±bevacizumab). The primary objective was event-free survival (EFS) evaluated by an independent radiological review committee.One hundred and fifty-four patients were randomised to receive chemotherapy alone (n = 80) or with bevacizumab (n = 74). At the data cut-off for the primary efficacy analysis, median EFS was 14.9 months (95% confidence interval [CI]: 10.8-35.9) with chemotherapy and 20.6 months (95% CI: 15.2-24.9) with bevacizumab plus chemotherapy (stratified hazard ratio [HR] = 0.93; 95% CI: 0.61-1.41; P = 0.72). The HR for EFS in patients with RMS (n = 103) was 1.24 (95% CI: 0.73-2.09) versus 0.64 (95% CI: 0.32-1.26) for those with NRSTS (n = 49). Objective response rate was 36.0% (95% CI: 25.2-47.9) with chemotherapy and 54.0% (95% CI: 40.9-66.6) with bevacizumab plus chemotherapy (difference of 18.0%; 95% CI: 0.6-35.3). There were no treatment-related deaths and no increased incidence of grade 3/4 toxicities with bevacizumab.The addition of bevacizumab to chemotherapy appeared tolerable in children and adolescents with metastatic RMS/NRSTS, but the primary end-point of EFS did not show statistically significant improvement.ClinicalTrials.gov, NCT00643565.