EURAMOS-1 (Good Response)

Background

Phase III EURAMOS-1 (Good Response Randomisation), international open-label RCT. N=567 randomized from resectable high-grade osteosarcoma with good histologic response (<10% viable tumour) to preoperative MAP (methotrexate 12 g/m², doxorubicin 75 mg/m², cisplatin 120 mg/m²). COG/COSS/EOI/SSG, 155 institutions. Of 2260 registered, 895 good responders; 567 randomized. Hypothesis: pegylated interferon alfa-2b maintenance improves EFS via immunomodulation. ISRCTN09268847.

Interventions and follow up

Arm A (MAP): Methotrexate + doxorubicin + cisplatin postoperatively ×29 wk
Arm B (MAP+IFN): MAP followed by pegylated interferon alfa-2b maintenance
Primary endpoint: Event-free survival (EFS)
mFollow up: Median 62 mo

Results

EFS: No significant difference MAP+IFN vs MAP (HR ~0.99, P>.5)
OS: No significant difference
IFN compliance: ~60% completed planned duration; compliance limited interpretation

Adverse events

MAP-related: mucositis, nephrotoxicity, hearing loss, myelosuppression — similar between arms
IFN-specific: fatigue, influenza-like syndrome, depression, elevated transaminases, injection-site reactions; poorly tolerated with frequent dose reductions/early discontinuation

Conclusions

Pegylated interferon alfa-2b maintenance added to MAP did not improve EFS or OS in good histologic responders. IFN maintenance cannot be recommended; MAP remains standard chemotherapy for resectable high-grade osteosarcoma.

Key Limitations

Poor IFN compliance (~60% completion) confounds interpretation of negative result; open-label design; EFS surrogate for OS; benefit in fully compliant subset cannot be excluded.

Clinical Context

Largest osteosarcoma RCT; MAP ×4 pre- and post-op endorsed by ASCO/ESMO as standard for resectable high-grade disease regardless of histologic response. No maintenance/intensification strategy has improved outcomes in good responders.

References