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). (September 2017)

• Record Type: Journal Article
• Authors: Chisholm, Julia C.; Merks, Johannes H.M.; Casanova, Michela; Bisogno, Gianni; Orbach, Daniel; Gentet, Jean-Claude; Thomassin-Defachelles, Anne-Sophie; Chastagner, Pascal; Lowis, Stephen; Ronghe, Milind; McHugh, Kieran; van Rijn, Rick R.; Hilton, Magalie; Bachir, Jeanette; Fürst-Recktenwald, Sabine; Geoerger, Birgit; Oberlin, Odile
• Is Part Of: European journal of cancer. Volume 83(2017)
• Page Start: 177
• Page End: 184
• Publication Date: 2017-09
• Subjects: Bevacizumab -- Metastatic soft tissue sarcoma -- NRSTS -- Paediatrics -- RMS; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2017.06.015
• Languages: English
• ISSNs: 0959-8049

Abstract

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 . Highlights: BERNIE evaluated the role of bevacizumab in childhood/adolescent metastatic soft tissue sarcoma. The addition of bevacizumab to the chemotherapy backbone appeared tolerable. The primary end-point of event-free survival did not show statistically significant improvement. These data do not support the use of bevacizumab in metastatic RMS.