Andrea Ferrari1, Johannes H M Merks2, Julia C Chisholm3, Daniel Orbach4, Bernadette Brennan5, Soledad Gallego6, Max M van Noesel7, Kieran McHugh8, Rick R van Rijn7, Mark N Gaze9, Helene Martelli10, Christophe Bergeron11, Nadege Corradini11, Veronique Minard-Colin12, Gianni Bisogno13, Birgit Geoerger12, Hubert N Caron14, Gian Luca De Salvo15, Michela Casanova16. 1. Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy. Electronic address: andrea.ferrari@istitutotumori.mi.it. 2. Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Department of Pediatric Oncology, Emma Children's Hospital-Academic Medical Center Amsterdam, the Netherlands. 3. Children and Young People's Unit, Royal Marsden Hospital, London, UK. 4. SIREDO Oncology Center, Institut Curie, PSL University, Paris, France. 5. Paediatric Oncology, Royal Manchester Children's Hospital, Manchester, UK. 6. Paediatric Oncology, Hospital Universitario Vall D'Hebron, Barcelona, Spain. 7. Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. 8. Radiology Department, Great Ormond Street Hospital for Children, London, UK. 9. Department of Oncology, University College London Hospitals NHS Foundation Trust, London, UK. 10. Department of Paediatric Surgery, Bicêtre Hospital, Hôpitaux Universitaires Paris-Sud, Assistance Publique Hôpitaux de Paris, Le Kremlin-Bicetre, France. 11. Department of Pediatric Oncology, Institut D'Hematologie et D'Oncologie Pédiatrique,/Centre Léon Bérard, Lyon, France. 12. Department of Pediatric and Adolescent Oncology, Gustave-Roussy, Cancer Campus, Université Paris-Saclay, Villejuif, France. 13. Hematology Oncology Division, Department of Women's and Children's Health, University of Padova, Padova, Italy. 14. IPODD, Pharma Development Oncology, Hoffmann-La Roche, Switzerland. 15. Clinical Trials and Biostatistics Unit, IRCCS Istituto Oncologico Veneto, Padova, Italy. 16. Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy.
Abstract
PURPOSE: We analysed the cohort of paediatric patients with metastatic non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) treated in the BERNIE protocol, i.e. open-label, multicentre, randomised phase II study evaluating the role of bevacizumab (BO20924/ITCC-006; ClinicalTrials.gov: NCT00643565). METHODS:Eligible patients were randomised 1:1 to add or not add bevacizumab to nine courses of intensive multi-drug chemotherapy, followed by 12-month maintenance chemotherapy (plus surgery and radiotherapy). The primary end-point was event-free survival (EFS); secondary objectives were objective response rate (ORR) and overall survival (OS). RESULTS: From 2008 and 2013, 49 NRSTS patients (out of 154 cases) were treated, 26 in the standard arm and 23 in the bevacizumab arm. ORR was seen in 10 out of 36 evaluable cases (27.7%), i.e. 4/18 standard arm cases and 6/18 bevacizumab arm cases. Two-year EFS was 27.3% (95% confidence interval [CI] 13.9-42.5) for all NRSTS patients, i.e. 34.9% (95% CI 14.6-56.2) for bevacizumab arm and 22.9% (95% CI 7.1-43.9) for standard arm (p-value = 0.19). Three-year OS (median follow-up 48.6 months) was 35.2%, with no differences in the two arms. Time to event and time to death were 16.3 and 17.2 months for bevacizumab arm and 2.1 and 7.6 months for standard arm, respectively. Patients not receiving any local treatment on primary disease had a worse outcome as compared to others. Treatment results were better for patients receiving surgical resection and worse for those who did not receive any specific treatment. CONCLUSION: The addition of the anti-angiogenic agent to the standard chemotherapy did not show statistically significant improvement in survival in metastatic NRSTS.
RCT Entities:
PURPOSE: We analysed the cohort of paediatric patients with metastatic non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) treated in the BERNIE protocol, i.e. open-label, multicentre, randomised phase II study evaluating the role of bevacizumab (BO20924/ITCC-006; ClinicalTrials.gov: NCT00643565). METHODS: Eligible patients were randomised 1:1 to add or not add bevacizumab to nine courses of intensive multi-drug chemotherapy, followed by 12-month maintenance chemotherapy (plus surgery and radiotherapy). The primary end-point was event-free survival (EFS); secondary objectives were objective response rate (ORR) and overall survival (OS). RESULTS: From 2008 and 2013, 49 NRSTSpatients (out of 154 cases) were treated, 26 in the standard arm and 23 in the bevacizumab arm. ORR was seen in 10 out of 36 evaluable cases (27.7%), i.e. 4/18 standard arm cases and 6/18 bevacizumab arm cases. Two-year EFS was 27.3% (95% confidence interval [CI] 13.9-42.5) for all NRSTSpatients, i.e. 34.9% (95% CI 14.6-56.2) for bevacizumab arm and 22.9% (95% CI 7.1-43.9) for standard arm (p-value = 0.19). Three-year OS (median follow-up 48.6 months) was 35.2%, with no differences in the two arms. Time to event and time to death were 16.3 and 17.2 months for bevacizumab arm and 2.1 and 7.6 months for standard arm, respectively. Patients not receiving any local treatment on primary disease had a worse outcome as compared to others. Treatment results were better for patients receiving surgical resection and worse for those who did not receive any specific treatment. CONCLUSION: The addition of the anti-angiogenic agent to the standard chemotherapy did not show statistically significant improvement in survival in metastatic NRSTS.
Authors: Andrea Ferrari; Bernadette Brennan; Michela Casanova; Nadege Corradini; Pablo Berlanga; Reineke A Schoot; Gema L Ramirez-Villar; Akmal Safwat; Gabriela Guillen Burrieza; Patrizia Dall'Igna; Rita Alaggio; Lisa Lyngsie Hjalgrim; Susanne Andrea Gatz; Daniel Orbach; Max M van Noesel Journal: Cancer Manag Res Date: 2022-09-23 Impact factor: 3.602
Authors: Carolina Bernauer; Y K Stella Man; Julia C Chisholm; Elise Y Lepicard; Simon P Robinson; Janet M Shipley Journal: Br J Cancer Date: 2020-10-27 Impact factor: 7.640