J Clin Oncol 2015 Jul 1;33(20):2279-87. Epub 2015 Jun 1.
Stefan S. Bielack, Klinikum Stuttgart-Olgahospital, Stuttgart; Mathias Werner, Helios Klinikum Emil von Behring; Per-Ulf Tunn, Helios Klinikum Berlin-Buch, Berlin; Knut Helmke, Altonaer Kinderkrankenhaus, Hamburg; Heribert Jürgens, Gabriele Calaminus, Joachim Gerss, and Trude Butterfass-Bahloul, Universitätsklinikum Münster, Münster; Peter Reichardt, Klinik für Interdisziplinäre Onkologie, Bad Saarow, Germany; Sigbjørn Smeland and Kirsten Sundby Hall, Oslo University Hospital; Kirsten Sundby Hall, Norwegian Radium Hospital, Oslo, Norway; Jeremy S. Whelan, University College London Hospitals; Gordana Jovic, Jane M. Hook, and Matthew R. Sydes, University College London; Beatrice Seddon and Maria Michelagnoli, University College Hospital, London; Bernadette Brennan, Christie Hospital and Royal Manchester Children's Hospital, Manchester; Susan Picton, Leeds University Hospital, Leeds, United Kingdom; Neyssa Marina, Stanford University Medical Center; Claudia Deffenbaugh, Lucille Salter Packard Children's Hospital, Palo Alto; Mark D. Krailo, Children's Oncology Group, Arcadia, CA; Mark Gebhardt and Allen Goorin, Dana-Farber Cancer Institute; Mark Gebhardt and Lisa A. Teot, Children's Hospital Boston, Boston, MA; Zsuzsanna Pápai, National Medical Center, Budapest, Hungary; James Meyer, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA; Helen Nadel, British Columbia Children's Hospital and University of British Columbia, Vancouver, British Columbia; Mark Bernstein, Dalhousie University, Halifax, Nova Scotia, Canada; R. Lor Randall, University of Utah, Salt Lake City, UT; Rajaram Nagarajan, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; G. Douglas Letson, H. Lee Moffit Cancer Center and Research Institute, Tampa, FL; Daniel Baumhoer, Universitätsspital Basel; Thomas Kühne, University Children's Hospital Basel, Basel, Switzerland; Leo Kager, St Anna's Children Hospital; Reinhard Windhager, Medica
Purpose: EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-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-α-2b (0.5 to 1.0 μg/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-α-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-α-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-α-2b and for stopping prematurely, respectively. Median IFN-α-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-α-2b and provided toxicity information reported grade ≥ 3 toxicity during IFN-α-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-α-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-α-2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN-α-2b or stopped prematurely. Long-term follow-up for events and survival continues.