EURAMOS-1
A Randomized Trial of the European and American Osteosarcoma Study Group to Optimize Treatment Strategies for Resectable Osteosarcoma Based on Histological Response to Pre-operative Chemotherapy
Phase 3N = 2,260NCT00134030
- Population
- Patients aged 40 years or younger with newly diagnosed, resectable high-grade osteosarcoma; 2260 registered
- Design
- All patients aged 40 years or younger with resectable high-grade osteosarcoma received preoperative MAP (methotrexate, doxorubicin, cisplatin). After surgery, patients with at least 10% viable tumour (poor response) were randomised 1:1 to postoperative MAP or MAP plus ifosfamide and etoposide (MAPIE); patients with less than 10% viable tumour (good response) were randomised to MAP or MAP followed by maintenance pegylated interferon alfa-2b. 2260 patients registered from 325 or 326 sites (the abstracts differ), 1334 randomised (618 poor responders, 716 good responders).
- Primary endpoint
- EFS
- Arms
- Poor responders: MAP (control, n = 310): Postoperative cisplatin, doxorubicin and high-dose methotrexate (MAP)
- Poor responders: MAPIE (experimental, n = 308): MAP plus high-dose ifosfamide and etoposide
- Good responders: MAP (control, n = 359): Four additional cycles of MAP
- Good responders: MAP plus pegylated interferon alfa-2b (experimental, n = 357): Four additional cycles of MAP followed by maintenance pegylated interferon alfa-2b
- People
- Marina NM, EURAMOS-1 investigators
Show the numbers
| Endpoint | Analysis | Poor responders: MAPIE / Good responders: MAP plus pegylated interferon alfa-2b | Poor responders: MAP / Good responders: MAP | Effect |
|---|---|---|---|---|
| EFSITT, poor responders (618 randomised) | primarymedian follow-up 62.1 monthsMarina 2016 | — | — | HR 0.98 (95% CI 0.78–1.23)MAPIE vs MAP. 307 EFS events (153 MAP, 154 MAPIE) and 193 deaths (101 MAP, 92 MAPIE). The abstract states that hazards were non-proportional (p=0.0003). |
| EFSGood responders who consented to randomisation (716) | primarymedian follow-up 44 monthsBielack 2015 | — | — | HR 0.83 (95% CI 0.61–1.12)P=.214MAP plus pegylated interferon alfa-2b vs MAP, adjusted Cox model; 174 EFS events (93 MAP, 81 MAP plus interferon). 3-year EFS for all 716 randomised patients was 76% (95% CI 72%-79%). Preplanned analysis time; follow-up continues. |
| Endpoint | Analysis | Poor responders: MAPIE / Good responders: MAP plus pegylated interferon alfa-2b | Poor responders: MAP / Good responders: MAP | Effect |
|---|---|---|---|---|
| EFSITT, poor responders (618 randomised) | primarymedian follow-up 62.1 monthsMarina 2016 | — | — | HR 0.98 (95% CI 0.78–1.23)MAPIE vs MAP. 307 EFS events (153 MAP, 154 MAPIE) and 193 deaths (101 MAP, 92 MAPIE). The abstract states that hazards were non-proportional (p=0.0003). |
| EFSGood responders who consented to randomisation (716) | primarymedian follow-up 44 monthsBielack 2015 | — | — | HR 0.83 (95% CI 0.61–1.12)P=.214MAP plus pegylated interferon alfa-2b vs MAP, adjusted Cox model; 174 EFS events (93 MAP, 81 MAP plus interferon). 3-year EFS for all 716 randomised patients was 76% (95% CI 72%-79%). Preplanned analysis time; follow-up continues. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| EFS | 0.98 | 0.78–1.23 |
| EFS | 0.83 | 0.61–1.12 |
Appears in
Sources
Marina NM, Smeland S, Bielack SS, Bernstein M, Jovic G, Krailo MD, et al. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. Lancet Oncol. 2016;17(10):1396-1408.
Bielack SS, Smeland S, Whelan JS, Marina N, Jovic G, Hook JM, et al. 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;33(20):2279-87.