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

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PURPOSE: EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-alpha-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy. PATIENTS AND METHODS: At diagnosis, patients age </= 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included >/= two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN-alpha-2b (0.5 to 1.0 mug/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary). RESULTS: Good response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN-alpha-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-alpha-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-alpha-2b and for stopping prematurely, respectively. Median IFN-alpha-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-alpha-2b and provided toxicity information reported grade >/= 3 toxicity during IFN-alpha-2b treatment. With median follow-up of 44 months, 3-year EFS for all 716 randomly assigned patients was 76% (95% CI, 72% to 79%); 174 EFS events were reported (MAP, n = 93; MAP plus IFN-alpha-2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P = .214) from an adjusted Cox model. CONCLUSION: At the preplanned analysis time, MAP plus IFN-alpha-2b was not statistically different from MAP alone. A considerable proportion of patients never