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
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 | - |
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