Integrated analysis of long-term growth and bone development in pediatric and adolescent patients receiving bevacizumab

Background: We conducted an integrated analysis of clinical data to describe long-term effects of bevacizumab on growth and bone development in pediatric and adolescent patients with solid tumors. Procedure: Clinical data were pooled from five phase I/II trials of bevacizumab versus chemotherapy: BERNIE, HERBY, and AVF4117s enrolled newly diagnosed patients, AVF3842s and AVF2771s enrolled patients with relapsed/refractory disease. Height, weight, body mass index (BMI), and bone-age data were pooled by treatment group. Growth charts were used to track and monitor growth in relation to a reference population of healthy children. Bone age was measured based on X-ray of the left hand and wrist. Analyses were exploratory/descriptive. Results: Overall, 268 patients received bevacizumab ± chemotherapy and 135 received chemotherapy alone. Baseline characteristics were generally balanced. Median duration of long-term follow-up was 41.8 months (range, 2.4-75.1) with bevacizumab and 22.9 months (range, 2.8-69.2) with chemotherapy alone. Patients had age-appropriate baseline height and weight. Mean height and weight percentiles decreased over time in both treatment groups, but remained within the normal range (height: mean standard deviation score [SDS] range −2 to +3; weight: mean SDS range −2 to +1). Similar trends were seen in BMI. A tendency for reduced growth velocity relative to the reference population was observed at 6 months and 1 year in both groups, but there was no additional decrease for patients receiving bevacizumab. Conclusion: Bevacizumab did not appear to have additional negative effects on growth or development of pediatric and adolescent patients with solid tumors

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)

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 656 months to <18 years were randomised to receive induction chemotherapy (four cycles of IVADo + five cycles of IVA, \ub1bevacizumab), surgery and/or radiotherapy, followed by maintenance chemotherapy (12 cycles of low-dose cyclophosphamide + vinorelbine, \ub1bevacizumab). 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\u201335.9) with chemotherapy and 20.6 months (95% CI: 15.2\u201324.9) with bevacizumab plus chemotherapy (stratified hazard ratio [HR] = 0.93; 95% CI: 0.61\u20131.41; P = 0.72). The HR for EFS in patients with RMS (n = 103) was 1.24 (95% CI: 0.73\u20132.09) versus 0.64 (95% CI: 0.32\u20131.26) for those with NRSTS (n = 49). Objective response rate was 36.0% (95% CI: 25.2\u201347.9) with chemotherapy and 54.0% (95% CI: 40.9\u201366.6) with bevacizumab plus chemotherapy (difference of 18.0%; 95% CI: 0.6\u201335.3). 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