BERNIE: Open-label, randomized, phase II study of bevacizumab plus chemotherapy in pediatric metastatic rhabdomyosarcoma (RMS) and non-rhabdomyosarcoma soft tissue sarcoma (NRSTS).

Authors

null

Julia C. Chisholm

The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom

Julia C. Chisholm , Johannes H. Merks , Michela Casanova , Gianni Bisogno , Daniel Orbach , Jean-Claude Gentet , Anne-Sophie Thomassin Defachelles , Pascal B. Chastagner , Steve Lowis , Milind Ronghe , Kieran McHugh , Rick R. van Rijn , Magalie Hilton , Jeanette Bachir , Sabine Fürst-Recktenwald , Birgit Geoerger , Odile Oberlin

Organizations

The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom, Academic Medical Center, Amsterdam, Netherlands, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Clinica di Oncoematologia Pediatrica, Università degli Studi di Padova, Padova, Italy, Institut Curie, Paris, France, Hôpital pour Enfants de La Timone, Marseille, France, Centre Oscar Lambret, Lille, France, Hôpital de Brabois Adultes, Vandoeuvre-Lès-Nancy, France, Bristol Royal Hospital for Children, Bristol, United Kingdom, Royal Hospital for Sick Children, Glasgow, United Kingdom, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom, F. Hoffmann-La Roche Ltd., Basel, Switzerland, Gustave Roussy, Villejuif, France, Institut Gustave Roussy, Villejuif, France

Research Funding

Pharmaceutical/Biotech Company

Background: Thephase II BERNIE study evaluated the role of bevacizumab as part of the multi-modality treatment of children and adolescents with metastatic RMS/NRSTS. Methods: Eligible patients aged ≥6 months and <18 years were randomized to receive 18 months of induction chemotherapy (4x 21-day cycles of IVADo [ifosfamide, vincristine, actinomycin-D, doxorubicin] + 5x cycles of IVA; ± bevacizumab 7.5mg/kg q3w) with local therapy, followed by maintenance chemotherapy (12x 28-day cycles of cyclophosphamide + vinorelbine; ± bevacizumab 5.0mg/kg q2w). The primary objective was independent review committee (IRC)-assessed event-free survival (EFS). Secondary objectives included: pharmacokinetics; safety; overall response rate (ORR); and overall survival (OS). Results: 154 patients were randomized to receive chemotherapy (n=80) or bevacizumab plus chemotherapy (n=74). Baseline characteristics were balanced. The cut-off for the results shown below was May 31, 2015, 19 months after the last patient was enrolled. Conclusions: The addition of bevacizumab to the chemotherapy backbone appeared tolerable and enhanced ORR in children and adolescents with metastatic RMS/NRSTS, but the primary and secondary efficacy endpoints were not met. Long-term observation continues. Clinical trial information: NCT00643565

Chemotherapy
(n=80)
Bevacizumab + chemo-
therapy (n=74)
Hazard ratio
(95% CI)
Median survival follow-up, months20.524.95-
Patients with an event, n (%)42 (52.5)51 (68.9)-
Median EFS by IRC, months14.920.60.93 (0.61−1.41); p=0.72
Median EFS by investigator, months12.518.90.71 (0.47−1.07); p=0.10
Median OS, months42.232.30.79 (0.49−1.26); p=0.32
ORR by IRC, %36.054.0Difference 18.0%
(95% Hauck-Anderson CI:
0.64−35.30); p=0.04
Grade 3/4 AEs (mainly hematologic),
% patients
10098.6-
Grade 3/4 AEs of special interest for
bevacizumab, % patients
12.712.7-
Deaths due to AEs, %00-

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Abstract Details

Meeting

2016 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Sarcoma

Track

Sarcoma

Sub Track

Soft Tissue Tumors

Clinical Trial Registration Number

NCT00643565

Citation

J Clin Oncol 34, 2016 (suppl; abstr 11054)

DOI

10.1200/JCO.2016.34.15_suppl.11054

Abstract #

11054

Poster Bd #

180

Abstract Disclosures