title: Lifetime effectiveness of mifamurtide addition to chemotherapy in nonmetastatic and metastatic osteosarcoma: a Markov process model analysis.
abstract: The mortality and progression rates in osteosarcoma differ depending on the presence of metastasis. A decision model would be useful for estimating long-term effectiveness of treatment with limited clinical trial data. The aim of this study was to explore the lifetime effectiveness of the addition of mifamurtide to chemotherapy for patients with metastatic and nonmetastatic osteosarcoma. The target population was osteosarcoma patients with or without metastasis. A Markov process model was used, whose time horizon was lifetime with a starting age of 13 years. There were five health states: disease-free (DF), recurrence, post-recurrence disease-free, post-recurrence disease-progression, and death. Transition probabilities of the starting state, DF, were calculated from the INT-0133 clinical trials for chemotherapy with and without mifamurtide. Quality-adjusted life-years (QALY) increased upon addition of mifamurtide to chemotherapy by 10.5 % (10.13 and 9.17 QALY with and without mifamurtide, respectively) and 45.2 % (7.23 and 4.98 QALY with and without mifamurtide, respectively) relative to the lifetime effectiveness of chemotherapy in nonmetastatic and metastatic osteosarcoma, respectively. Life-years gained (LYG) increased by 10.1 % (13.10 LYG with mifamurtide and 11.90 LYG without mifamurtide) in nonmetastatic patients and 42.2 % (9.43 LYG with mifamurtide and 6.63 LYG without mifamurtide) in metastatic osteosarcoma patients. The Markov model analysis showed that chemotherapy with mifamurtide improved the lifetime effectiveness compared to chemotherapy alone in both nonmetastatic and metastatic osteosarcoma. Relative effectiveness of the therapy was higher in metastatic than nonmetastatic osteosarcoma over lifetime. However, absolute lifetime effectiveness was higher in nonmetastatic than metastatic osteosarcoma.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 440-746, Republic of Korea.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Song
authors.affiliation: Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Republic of Korea.
authors.forename: Jun Ah
authors.initials: JA
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea.
authors.forename: Euna
authors.initials: E
authors.lastname: Han
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 440-746, Republic of Korea. ekyung@skku.edu.
authors.forename: Eui-Kyung
authors.initials: EK
authors.lastname: Lee
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004358:Drug Therapy; D006801:Humans; D008390:Markov Chains; D015233:Models, Statistical; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D010714:Phosphatidylethanolamines / Q000627:therapeutic use*
chemical_list: D010714:Phosphatidylethanolamines; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine
keywords: Decision analysis; Markov model; Mifamurtide; Osteosarcoma; Quality-adjusted life-years
references.citation: Expert Opin Pharmacother. 2011 Feb;12 (2):285-92
references.pmid: 21226638
references.citation: J Clin Oncol. 2008 Feb 1;26(4):633-8
references.pmid: 18235123
references.citation: J Clin Oncol. 2005 Mar 20;23(9):2004-11
references.pmid: 15774791
references.citation: Value Health. 2013 Dec;16(8):1123-32
references.pmid: 24326165
references.citation: Tumour Biol. 2014 Sep;35(9):8771-9
references.pmid: 24874050
references.citation: Cancer. 2009 Nov 15;115(22):5339-48
references.pmid: 19637348
references.citation: Ann Oncol. 2009 May;20 Suppl 4:137-9
references.pmid: 19454435
references.citation: J Clin Oncol. 2002 Feb 1;20(3):776-90
references.pmid: 11821461
references.citation: Pediatr Blood Cancer. 2009 Mar;52(3):340-5
references.pmid: 19021220
references.citation: J Clin Oncol. 2009 Feb 1;27(4):557-65
references.pmid: 19075282
references.citation: J Clin Oncol. 2005 Jan 20;23(3):559-68
references.pmid: 15659502