- Email: [email protected]
Zoledronate Does not Reduce the Risk of Treatment Failure in Osteosarcoma: Results of the French Multicentre Os2006 Randomised Trial
Annals of Oncology 25 (Supplement 4): iv494–iv510, 2014 doi:10.1093/annonc/mdu354.2
sarcoma 1413O
ZOLEDRONATE DOES NOT REDUCE THE RISK OF TREATMENT FAILURE IN OSTEOSARCOMA: RESULTS OF THE FRENCH MULTICENTRE OS2006 RANDOMISED TRIAL
abstracts
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv494/2242118 by guest on 25 October 2019
S. Piperno-Neumann1, M. Le Deley2, F. Rédini3, P. Marec-Bérard4, H. Pacquement5, C. Lervat6, J. Gentet7, N. Entz-Werlé8, A. Italiano9, N. Corradini10, E. Bompas11, N. Penel12, M. Tabone13, G. De Pinieux14, P. Petit15, K. Buffard16, J. Blay17, L. Brugières18 1 Medical Oncology, Institut Curie, Paris, FRANCE 2 Biostatistics, Gustave Roussy, Villejuif, FRANCE 3 INSERM, Umr957, Faculté de Médecine, EA 3822, Nantes, FRANCE 4 Pediatric Oncology, Institut d’Hémato-Oncologie Pédiatrique, Lyon, FRANCE 5 Pediatric Oncology, Institut Curie, Paris, FRANCE 6 Pediatric Oncology, Centre Oscar-Lambret, Lille, FRANCE 7 Pediatric Oncology, Hôpital de la Timone, Marseille, FRANCE 8 Pediatric Oncology, CHRU, Strasbourg, FRANCE 9 Medical Oncology, Institut Bergonié, Bordeaux, FRANCE 10 Pediatric Oncology, CHU, Nantes, FRANCE 11 Oncology, ICO Institut de Cancerologie de l’Ouest René Gauducheau, Nantes, FRANCE 12 Medical Oncology, Centre Oscar Lambret, Lille, FRANCE 13 Pediatric Oncology, Hôpital Trousseau, Paris, FRANCE 14 Pathology, Hôpital Trousseau, Tours, FRANCE 15 Radiology, Hopital de la Timone, Marseille, FRANCE 16 Sarcoma Group, Unicancer, Paris, FRANCE 17 Medical Oncology, Centre Léon-Berard, Lyon, FRANCE 18 Pediatric Oncology, Gustave Roussy, Villejuif, FRANCE
Aim: Based on anti-tumour effect of zoledronate in vitro and in experimental models of rat osteosarcoma, we assessed whether zoledronate (Z) in combination with chemotherapy and surgery improved Event-Free Survival (EFS) in children and adult patients ( pts) with osteosarcoma. Methods: Experimental treatment consisted of 10 Z-injections (4 pre and 6 postoperative), 4 mg/injection in adults, 0.05 mg/kg/injection in younger pts. Chemotherapy included methotrexate-etoposide-ifosfamide +/-adriamycine-cisplatin in children/adolescents, and doxorubicin-ifosfamide/doxorubicin-ifosfamidecisplatinum in adults. Balanced randomisation between Z+arm and Z-arm was stratified by center, age, chemotherapy type and risk group (localised resectable disease versus unresectable primary and/or metastases). The study was planned as an open-label superiority trial, with 3 interim analyses (early stopping for efficacy or harm) disclosed to an independent safety monitoring board (DSMB). 470 pts (170 events) were required to achieve an 80%-power to detect a 13%-improvement of 3-year EFS (H1: 55% versus 68%, HR(event)=0.65) with zoledronate (2-sided alpha=0.05). Results: A second interim analysis was performed after 318 pts (82% with a localised and resectable tumour) have been recruited between April 2007 and February 2014: 158 Z- and 160 Z+. No significant increase in toxicity was found in Z+, except expected hypocalcemia grade 2-4 ( p<0.0001). With a median follow-up of 3.1 years, 106 events and 58 deaths were reported, including one treatment-related death. The risk of treatment failure was not reduced in Z+ compared to Z-: HR(event)=1.31 [0.79–2.18], p=0.17; HR(death)=1.42 [0.70–2.88], p=0.21. Results were similar after exclusion of eight Z+patients who had received 0 or1 zoledronate injection, and were homogeneous across the randomisation strata. Futility analysis, performed on DSMB request, showed that the probability of demonstrating a benefit for Z+ was <0.0001. Following DSMB recommendation, the trial steering committee decided to stop accrual in the trial. Conclusions: With current follow-up, the addition of zoledronate to chemotherapy did not reduce the risk of failure in osteosarcoma patients. Disclosure: All authors have declared no conflicts of interest.
sarcoma 1413O
ZOLEDRONATE DOES NOT REDUCE THE RISK OF TREATMENT FAILURE IN OSTEOSARCOMA: RESULTS OF THE FRENCH MULTICENTRE OS2006 RANDOMISED TRIAL
abstracts
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv494/2242118 by guest on 25 October 2019
S. Piperno-Neumann1, M. Le Deley2, F. Rédini3, P. Marec-Bérard4, H. Pacquement5, C. Lervat6, J. Gentet7, N. Entz-Werlé8, A. Italiano9, N. Corradini10, E. Bompas11, N. Penel12, M. Tabone13, G. De Pinieux14, P. Petit15, K. Buffard16, J. Blay17, L. Brugières18 1 Medical Oncology, Institut Curie, Paris, FRANCE 2 Biostatistics, Gustave Roussy, Villejuif, FRANCE 3 INSERM, Umr957, Faculté de Médecine, EA 3822, Nantes, FRANCE 4 Pediatric Oncology, Institut d’Hémato-Oncologie Pédiatrique, Lyon, FRANCE 5 Pediatric Oncology, Institut Curie, Paris, FRANCE 6 Pediatric Oncology, Centre Oscar-Lambret, Lille, FRANCE 7 Pediatric Oncology, Hôpital de la Timone, Marseille, FRANCE 8 Pediatric Oncology, CHRU, Strasbourg, FRANCE 9 Medical Oncology, Institut Bergonié, Bordeaux, FRANCE 10 Pediatric Oncology, CHU, Nantes, FRANCE 11 Oncology, ICO Institut de Cancerologie de l’Ouest René Gauducheau, Nantes, FRANCE 12 Medical Oncology, Centre Oscar Lambret, Lille, FRANCE 13 Pediatric Oncology, Hôpital Trousseau, Paris, FRANCE 14 Pathology, Hôpital Trousseau, Tours, FRANCE 15 Radiology, Hopital de la Timone, Marseille, FRANCE 16 Sarcoma Group, Unicancer, Paris, FRANCE 17 Medical Oncology, Centre Léon-Berard, Lyon, FRANCE 18 Pediatric Oncology, Gustave Roussy, Villejuif, FRANCE
Aim: Based on anti-tumour effect of zoledronate in vitro and in experimental models of rat osteosarcoma, we assessed whether zoledronate (Z) in combination with chemotherapy and surgery improved Event-Free Survival (EFS) in children and adult patients ( pts) with osteosarcoma. Methods: Experimental treatment consisted of 10 Z-injections (4 pre and 6 postoperative), 4 mg/injection in adults, 0.05 mg/kg/injection in younger pts. Chemotherapy included methotrexate-etoposide-ifosfamide +/-adriamycine-cisplatin in children/adolescents, and doxorubicin-ifosfamide/doxorubicin-ifosfamidecisplatinum in adults. Balanced randomisation between Z+arm and Z-arm was stratified by center, age, chemotherapy type and risk group (localised resectable disease versus unresectable primary and/or metastases). The study was planned as an open-label superiority trial, with 3 interim analyses (early stopping for efficacy or harm) disclosed to an independent safety monitoring board (DSMB). 470 pts (170 events) were required to achieve an 80%-power to detect a 13%-improvement of 3-year EFS (H1: 55% versus 68%, HR(event)=0.65) with zoledronate (2-sided alpha=0.05). Results: A second interim analysis was performed after 318 pts (82% with a localised and resectable tumour) have been recruited between April 2007 and February 2014: 158 Z- and 160 Z+. No significant increase in toxicity was found in Z+, except expected hypocalcemia grade 2-4 ( p<0.0001). With a median follow-up of 3.1 years, 106 events and 58 deaths were reported, including one treatment-related death. The risk of treatment failure was not reduced in Z+ compared to Z-: HR(event)=1.31 [0.79–2.18], p=0.17; HR(death)=1.42 [0.70–2.88], p=0.21. Results were similar after exclusion of eight Z+patients who had received 0 or1 zoledronate injection, and were homogeneous across the randomisation strata. Futility analysis, performed on DSMB request, showed that the probability of demonstrating a benefit for Z+ was <0.0001. Following DSMB recommendation, the trial steering committee decided to stop accrual in the trial. Conclusions: With current follow-up, the addition of zoledronate to chemotherapy did not reduce the risk of failure in osteosarcoma patients. Disclosure: All authors have declared no conflicts of interest.