Editor’s Note: A previous version of this article incorrectly referred to the treatment arm of this study as MAP; MAPIE, not MAP, failed to improve responses in this setting.

The addition of ifosfamide and etoposide to adjuvant cisplatin, doxorubicin, and high-dose methotrexate (MAP) did not improve event-free survival of patients with newly diagnosed, high-grade osteosarcoma, who respond poorly to neoadjuvant chemotherapy, according to a study published in The Lancet Oncology.1

For this open-label, phase 3 EURAMOS-1 trial, investigators enrolled 618 patients aged 40 years or younger with newly diagnosed osteosarcoma, each of whom had a poor response to preoperative chemotherapy.

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After resection, participants were randomly assigned 1:1 to receive MAP or MAP plus ifosfamide and etoposide (MAPIE).

With a median follow-up of 62.1 months, there was no significant difference in event-free survival between the 2 treatment arms (hazard ratio, 0.98; 95% CI, 0.78-1.23).

Patients treated with MAPIE experienced higher rates of grade non-hematologic toxicity than those in the MAP group, though rates of grade 3 to 4 neutropenia and thrombocytopenia were similar between the groups.

One patient in the MAP arm died due to treatment-related infection, and 1 patient died as a result of left ventricular systolic dysfunction in the MAPIE arm, likely due to study treatment.

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The findings suggest that adjuvant MAP chemotherapy should be the standard of care for these patients who have a poor response to preoperative chemotherapy, but new treatment strategies are needed to improve clinical outcomes in this setting.


  1. Marina NM, Smeland S, Bielack SS, 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 Aug 25. doi: 10.1016/S1470-2045(16)30214-5 [Epub ahead of print]