In a Japanese trial (JCOG0905) reported in the Journal of Clinical Oncology, Hiraga et al found no disease-free survival benefit with the addition of a higher dose of ifosfamide to methotrexate, doxorubicin, and cisplatin (MAP) in patients with newly diagnosed high-grade osteosarcoma with poor response to preoperative chemotherapy.
While the EURAMOS-1 trial previously demonstrated that the addition of ifosfamide plus etoposide to postoperative MAP did not improve prognosis for poor responders, other studies suggested that adding a higher dose of ifosfamide alone, without etoposide, to neoadjuvant chemotherapy might prove beneficial. Therefore, the JCOG0905 trial was conducted “to confirm whether the addition of a cumulative total dose of [ifosfamide] at 90 g/m2 … to poor responders would improve their prognosis, outweighing the disadvantages of additional adverse events and extended treatment duration.”
Study Details
In the multicenter open-label trial, patients aged ≤ 50 years received two cycles of preoperative MAP and underwent resection between February 2010 and August 2020. A total of 103 patients with poor response at resection were randomly assigned to continue MAP (n = 51) or receive MAP plus ifosfamide (n = 52). Ifosfamide was administered at 15 g/m2 (3 g/m2 once daily on days 1–5) for six cycles, for a cumulative total dose of 90 g/m2. The primary endpoint of the study was disease-free survival.
Key Findings
At a median follow-up of 67.1 months, disease-free survival events occurred in 20 of 52 patients in the MAP plus ifosfamide group vs 18 of 51 in the MAP group (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 0.55–1.98, P = .55), with a 3-year disease-free survival of 64.3% in both groups.
Death occurred in 15 patients in the MAP plus ifosfamide group vs 11 patients in the MAP group (HR = 1.48, 95% CI = 0.68–3.22), with 3-year overall survival of 78.8% vs 86.5%.
Adverse events led to discontinuation of treatment in nine patients in the MAP plus ifosfamide group and none in the MAP group.
The investigators concluded: “Evidence from JCOG0905 does not support the addition of [ifosfamide] for patients with [poor response to preoperative chemotherapy].”
Hiroaki Hiraga, PhD, of NHO Hokkaido Cancer Center, Sapporo, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Ministry of Health, Labor and Welfare, Japan Agency for Medical Research and Development, and others. For full disclosures of the study authors, visit ascopubs.org.
