Osteosarcoma - null regimens

The purpose of this page is to provide references to "null therapy" such as placebo and observation. These references provide further insight into the historical development of the treatment landscape. See the main osteosarcoma page for regimens that include active anticancer treatment.

Adjuvant therapy

Observation

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Eilber et al. 1987	1981-1984	Randomized (C)	M-BCD	Seems to have inferior OS
Link et al. 1986	1982-1984	Phase 3 (C)	MA-BCD/AP	Inferior RFS

No further treatment.

Preceding treatment

• Eilber et al. 1987: Neoadjuvant M-BCD, then surgery, with good response
• Link et al. 1986: Surgery

References

1. Link MP, Goorin AM, Miser AW, Green AA, Pratt CB, Belasco JB, Pritchard J, Malpas JS, Baker AR, Kirkpatrick JA, Ayala AG, Shuster JJ, Abelson HT, Simone JV, Vietti TJ. The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med. 1986 Jun 19;314(25):1600-6. link to original article PubMed
2. Eilber F, Giuliano A, Eckardt J, Patterson K, Moseley S, Goodnight J. Adjuvant chemotherapy for osteosarcoma: a randomized prospective trial. J Clin Oncol. 1987 Jan;5(1):21-6. link to original article PubMed
   1. Update: Bernthal NM, Federman N, Eilber FR, Nelson SD, Eckardt JJ, Eilber FC, Tap WD. Long-term results (>25 years) of a randomized, prospective clinical trial evaluating chemotherapy in patients with high-grade, operable osteosarcoma. Cancer. 2012 Dec 1;118(23):5888-93. Epub 2012 May 30. link to original article PubMed

Maintenance after upfront therapy

Observation

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Bielack et al. 2015 (EURAMOS-1 good response)	2005-2011	Phase 3 (C)	Interferon alfa-2b	Did not meet primary endpoint of EFS

No further treatment.

Preceding treatment

• Neoadjuvant MAP x 2, then surgery, then adjuvant MAP x 2, then adjuvant MA x 2

References

1. EURAMOS-1 good response: Bielack SS, Smeland S, Whelan JS, Marina N, Jovic G, Hook JM, Krailo MD, Gebhardt M, Pápai Z, Meyer J, Nadel H, Randall RL, Deffenbaugh C, Nagarajan R, Brennan B, Letson GD, Teot LA, Goorin A, Baumhoer D, Kager L, Werner M, Lau CC, Sundby Hall K, Gelderblom H, Meyers P, Gorlick R, Windhager R, Helmke K, Eriksson M, Hoogerbrugge PM, Schomberg P, Tunn PU, Kühne T, Jürgens H, van den Berg H, Böhling T, Picton S, Renard M, Reichardt P, Gerss J, Butterfass-Bahloul T, Morris C, Hogendoorn PC, Seddon B, Calaminus G, Michelagnoli M, Dhooge C, Sydes MR, Bernstein M; EURAMOS-1 investigators. Methotrexate, doxorubicin, and cisplatin (MAP) plus maintenance pegylated interferon alfa-2b versus MAP alone in patients with resectable high-grade osteosarcoma and good histologic response to preoperative map: first results of the EURAMOS-1 good response randomized controlled trial. J Clin Oncol. 2015 Jul 10;33(20):2279-87. Epub 2015 Jun 1. link to original article link to PMC article PubMed

Relapsed, refractory, or metastatic, subsequent lines

Placebo

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Davis et al. 2019 (SARC024)	2014-2018	Randomized Phase 2 (C)	Regorafenib	Inferior PFS

No active antineoplastic treatment.

References

1. SARC024: Davis LE, Bolejack V, Ryan CW, Ganjoo KN, Loggers ET, Chawla S, Agulnik M, Livingston MB, Reed D, Keedy V, Rushing D, Okuno S, Reinke DK, Riedel RF, Attia S, Mascarenhas L, Maki RG. Randomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma. J Clin Oncol. 2019 Jun 1;37(16):1424-1431. Epub 2019 Apr 23. link to original article link to PMC article PubMed NCT02048371