EURAMOS-1 (Poor Response / MAPIE)

Background

Phase III EURAMOS-1 (Poor Response Randomisation), international open-label RCT. N=618 randomized from resectable high-grade osteosarcoma with poor histologic response (≥10% viable tumour) to preoperative MAP. COG/COSS/EOI/SSG. Of 2260 registered, ~1365 poor responders; 618 randomized. Hypothesis: adding ifosfamide + etoposide (MAPIE) overcomes adverse prognosis and improves EFS. ISRCTN09268847.

Interventions and follow up

Arm A (MAP): Methotrexate + doxorubicin + cisplatin postoperatively
Arm B (MAPIE): MAP + ifosfamide + etoposide (intensified)
Primary endpoint: Event-free survival (EFS)
mFollow up: Median 53 mo

Results

EFS: HR 0.98, 95% CI 0.71–1.36, P=.72 — not significant
OS: No significant difference
3-yr EFS: ~52% (MAPIE) vs ~50% (MAP)

Adverse events

Grade ≥3 AEs: significantly higher with MAPIE
Hematologic: neutropenia, thrombocytopenia markedly worse with MAPIE; febrile neutropenia more frequent
Ototoxicity: similar
Treatment-related deaths: few but numerically more with MAPIE

Conclusions

MAPIE did not improve EFS or OS vs MAP in poor-responding high-grade osteosarcoma (HR 0.98, P=.72) with significantly increased toxicity. Poor histologic response remains a major adverse prognostic factor with no beneficial intensification; MAP remains standard regardless of response.

Key Limitations

Open-label; EFS surrogate endpoint; substantial added toxicity reduced deliverable dose intensity of MAPIE; response-adapted strategy assumption (histology predicts intensification benefit) not validated.

Clinical Context

Definitively closed the question of treatment intensification for poor responders. ASCO/ESMO endorse standard MAP for all histologic-response groups; no benefit to escalating chemotherapy based on necrosis. Reinforces unmet need for novel agents in high-risk osteosarcoma.

References