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)

Eur J Cancer. 2017 Sep;83:177-184. doi: 10.1016/j.ejca.2017.06.015. Epub 2017 Aug 23.

Abstract

Purpose: 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).

Patients and methods: 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.

Results: 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov, NCT00643565.

Keywords: Bevacizumab; Metastatic soft tissue sarcoma; NRSTS; Paediatrics; RMS.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / adverse effects
  • Bevacizumab / therapeutic use*
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Humans
  • Induction Chemotherapy / methods
  • Infant
  • Maintenance Chemotherapy / methods
  • Male
  • Sarcoma / drug therapy*
  • Soft Tissue Neoplasms / drug therapy*
  • Soft Tissue Neoplasms / pathology

Substances

  • Angiogenesis Inhibitors
  • Bevacizumab

Associated data

  • ClinicalTrials.gov/NCT00643565
  • ClinicalTrials.gov/NCT00643565