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

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).

Author information

1
Children and Young People's Unit, The Royal Marsden NHS Foundation Trust, Surrey, UK. Electronic address: julia.chisholm@rmh.nhs.uk.
2
Department of Pediatric Oncology, Emma Children's Hospital-Academic Medical Center (EKZ-AMC), Amsterdam, The Netherlands. Electronic address: j.h.merks@amc.uva.nl.
3
Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
4
Clinica di Oncoematologia Pediatrica, Università degli Studi di Padova, Padova, Italy.
5
Pediatric Adolescent and Young Adult Department, Institut Curie, Paris, France.
6
Service d'Hématologie et Oncologie Pédiatrique, Hôpital pour Enfants de La Timone, Marseille, France.
7
Pediatric Oncology Department, Centre Oscar Lambret, Lille, France.
8
Pediatric Oncology Department, Hôpital de Brabois Enfants, Vandœuvre-lès-Nancy, France.
9
Department of Paediatric and Adolescent Oncology, Bristol Royal Hospital for Children, Bristol, UK.
10
Department of Paediatric Oncology, Royal Hospital for Sick Children, Glasgow, UK.
11
Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
12
Department of Pediatric Radiology, Emma Children's Hospital-Academic Medical Center (EKZ-AMC), Amsterdam, The Netherlands.
13
Department of Statistics, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
14
Department of Oncology, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
15
Department of Pediatric and Adolescent Oncology, Gustave Roussy, Villejuif, France.

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

PMID:
28738258
DOI:
10.1016/j.ejca.2017.06.015
[Indexed for MEDLINE]

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