Improved osteosarcoma survival with addition of mifamurtide to conventional chemotherapy – Observational prospective single institution analysis
Purpose: Conventional osteosarcoma is an orphan disease. Current treatment approaches include combining a three drug chemotherapy schedule and surgery. The 3- and 5-year event-free survival (EFS) in localized disease is roughly 65 and 60%, respectively. The registration study of mifamurtide reported...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-06-01
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| Series: | Journal of Bone Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212137421000166 |
| _version_ | 1818669367732207616 |
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| author | Peter Múdry Michal Kýr Ondřej Rohleder Michal Mahdal Iva Staniczková Zambo Marta Ježová Tomáš Tomáš Jaroslav Štěrba |
| author_facet | Peter Múdry Michal Kýr Ondřej Rohleder Michal Mahdal Iva Staniczková Zambo Marta Ježová Tomáš Tomáš Jaroslav Štěrba |
| author_sort | Peter Múdry |
| collection | DOAJ |
| description | Purpose: Conventional osteosarcoma is an orphan disease. Current treatment approaches include combining a three drug chemotherapy schedule and surgery. The 3- and 5-year event-free survival (EFS) in localized disease is roughly 65 and 60%, respectively. The registration study of mifamurtide reported survival benefit, but some methodological controversies have been insufficient for FDA market authorization in contrast to EMA. Methods: prospective single centre survival analysis of a mifamurtide addition to conventional therapy in 23 patients over a 5.5 year enrolment period is reported and compared to a historical control of 26 patient with localized disease. Bias arising from observational methodology was addressed using Landmark analysis and time-dependent Cox models. Blood count dynamics were analysed during the treatment. Results: The adverse event profile was as expected with no dose limiting toxicities. There were no local relapses observed, one patient died in the first complete remission due to doxorubicin cardiotoxicity, one patient had pulmonary metastatic relapse. The observed 3- and 5-year EFS was 87.4% (CI 72.4–100%) and 87.4% (CI 72.4–100%), progression free survival (PFS) was 92.9% (CI 80.3–100%) and 92.9% (CI 80.3–100%), overall survival was 94.1% (CI 83.6–100) and 80.7% (CI 58.3–100), respectively. Comparison to the historical control showed statistically significant better PFS for mifamurtide patients (Landmark analysis; p = 0.044). Risk of progression was 5-times lower for the mifamurtide group (Cox model; HR 0.21, p = 0.136). Only subtle differences in lymphocyte counts were observed across treatment. Conclusion: the PFS benefit of mifamurtide is reported herein. The addition of mifamurtide could be considered as a best treatment option for localized osteosarcoma. |
| first_indexed | 2024-12-17T06:51:06Z |
| format | Article |
| id | doaj.art-d2c6f7ddce29434c93d6a72a9563cdf9 |
| institution | Directory Open Access Journal |
| issn | 2212-1374 |
| language | English |
| last_indexed | 2024-12-17T06:51:06Z |
| publishDate | 2021-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Bone Oncology |
| spelling | doaj.art-d2c6f7ddce29434c93d6a72a9563cdf92022-12-21T21:59:36ZengElsevierJournal of Bone Oncology2212-13742021-06-0128100362Improved osteosarcoma survival with addition of mifamurtide to conventional chemotherapy – Observational prospective single institution analysisPeter Múdry0Michal Kýr1Ondřej Rohleder2Michal Mahdal3Iva Staniczková Zambo4Marta Ježová5Tomáš Tomáš6Jaroslav Štěrba7Department of Paediatric Oncology, University Hospital Brno and School of Medicine, Masaryk University, Cernopolni 9, Brno 613 00, Czech Republic; International Clinical Research Centre, St. Anne's University Hospital Brno, Pekarska 53, Brno 656 91, Czech Republic; Corresponding author at: Department of Paediatric Oncology, University Hospital Brno and School of Medicine Masaryk University, Cernopolni 9, 613 00 Brno, Czech Republic.Department of Paediatric Oncology, University Hospital Brno and School of Medicine, Masaryk University, Cernopolni 9, Brno 613 00, Czech Republic; International Clinical Research Centre, St. Anne's University Hospital Brno, Pekarska 53, Brno 656 91, Czech RepublicDepartment of Paediatric Oncology, University Hospital Brno and School of Medicine, Masaryk University, Cernopolni 9, Brno 613 00, Czech Republic; International Clinical Research Centre, St. Anne's University Hospital Brno, Pekarska 53, Brno 656 91, Czech Republic1st Department of Orthopaedics, St. Annés University Hospital Brno and School of Medicine, Masaryk University, Pekarska 53, Brno 613 00, Czech Republic1st Department of Pathology, St. Anne’s University Hospital Brno and School of Medicine, Masaryk University, Pekarska 53, Brno 613 00, Czech RepublicDepartment of Pathology, University Hospital Brno and School of Medicine, Masaryk University, Jihlavska 20, Brno 625 00, Czech Republic1st Department of Orthopaedics, St. Annés University Hospital Brno and School of Medicine, Masaryk University, Pekarska 53, Brno 613 00, Czech RepublicDepartment of Paediatric Oncology, University Hospital Brno and School of Medicine, Masaryk University, Cernopolni 9, Brno 613 00, Czech Republic; International Clinical Research Centre, St. Anne's University Hospital Brno, Pekarska 53, Brno 656 91, Czech RepublicPurpose: Conventional osteosarcoma is an orphan disease. Current treatment approaches include combining a three drug chemotherapy schedule and surgery. The 3- and 5-year event-free survival (EFS) in localized disease is roughly 65 and 60%, respectively. The registration study of mifamurtide reported survival benefit, but some methodological controversies have been insufficient for FDA market authorization in contrast to EMA. Methods: prospective single centre survival analysis of a mifamurtide addition to conventional therapy in 23 patients over a 5.5 year enrolment period is reported and compared to a historical control of 26 patient with localized disease. Bias arising from observational methodology was addressed using Landmark analysis and time-dependent Cox models. Blood count dynamics were analysed during the treatment. Results: The adverse event profile was as expected with no dose limiting toxicities. There were no local relapses observed, one patient died in the first complete remission due to doxorubicin cardiotoxicity, one patient had pulmonary metastatic relapse. The observed 3- and 5-year EFS was 87.4% (CI 72.4–100%) and 87.4% (CI 72.4–100%), progression free survival (PFS) was 92.9% (CI 80.3–100%) and 92.9% (CI 80.3–100%), overall survival was 94.1% (CI 83.6–100) and 80.7% (CI 58.3–100), respectively. Comparison to the historical control showed statistically significant better PFS for mifamurtide patients (Landmark analysis; p = 0.044). Risk of progression was 5-times lower for the mifamurtide group (Cox model; HR 0.21, p = 0.136). Only subtle differences in lymphocyte counts were observed across treatment. Conclusion: the PFS benefit of mifamurtide is reported herein. The addition of mifamurtide could be considered as a best treatment option for localized osteosarcoma.http://www.sciencedirect.com/science/article/pii/S2212137421000166OsteosarcomaMifamurtideSurvivalSingle institution analysisComparative analysis |
| spellingShingle | Peter Múdry Michal Kýr Ondřej Rohleder Michal Mahdal Iva Staniczková Zambo Marta Ježová Tomáš Tomáš Jaroslav Štěrba Improved osteosarcoma survival with addition of mifamurtide to conventional chemotherapy – Observational prospective single institution analysis Journal of Bone Oncology Osteosarcoma Mifamurtide Survival Single institution analysis Comparative analysis |
| title | Improved osteosarcoma survival with addition of mifamurtide to conventional chemotherapy – Observational prospective single institution analysis |
| title_full | Improved osteosarcoma survival with addition of mifamurtide to conventional chemotherapy – Observational prospective single institution analysis |
| title_fullStr | Improved osteosarcoma survival with addition of mifamurtide to conventional chemotherapy – Observational prospective single institution analysis |
| title_full_unstemmed | Improved osteosarcoma survival with addition of mifamurtide to conventional chemotherapy – Observational prospective single institution analysis |
| title_short | Improved osteosarcoma survival with addition of mifamurtide to conventional chemotherapy – Observational prospective single institution analysis |
| title_sort | improved osteosarcoma survival with addition of mifamurtide to conventional chemotherapy observational prospective single institution analysis |
| topic | Osteosarcoma Mifamurtide Survival Single institution analysis Comparative analysis |
| url | http://www.sciencedirect.com/science/article/pii/S2212137421000166 |
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