BERNIE: Open-label, Randomized, Phase II Study of Bevacizumab Plus Chemotherapy in Pediatric Metastatic Rhabdomyosarcoma (RMS) and Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS).

11054 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, months 20.5 24.95 - Patients with an event, n (%) 42 (52.5) 51 (68.9) - Median EFS by IRC, months 14.9 20.6 0.93 (0.61−1.41); p=0.72 Median EFS by investigator, months 12.5 18.9 0.71 (0.47−1.07); p=0.10 Median OS, months 42.2 32.3 0.79 (0.49−1.26); p=0.32 ORR by IRC, % 36.0 54.0 Difference 18.0% (95% Hauck-Anderson CI: 0.64−35.30); p=0.04 Grade 3/4 AEs (mainly hematologic), % patients 100 98.6 - Grade 3/4 AEs of special interest for bevacizumab, % patients 12.7 12.7 - Deaths due to AEs, % 0 0 -