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

Stefan S. Bielack; Sigbjørn Smeland; Jeremy S. Whelan; Neyssa Marina; Gordana Jovic; Jane M. Hook; Mark D. Krailo; Mark Gebhardt; Zsuzsanna Pápai; James Meyer; Helen Nadel; R. Lor Randall; Claudia Deffenbaugh; Rajaram Nagarajan; Bernadette Brennan; G. Douglas Letson; Lisa A. Teot; Allen Goorin; Daniel Baumhoer; Leo Kager; Mathias Werner; Ching C. Lau; Kirsten Sundby Hall; Hans Gelderblom; Paul Meyers; Richard Gorlick; Reinhard Windhager; Knut Helmke; Mikael Eriksson; Peter M. Hoogerbrugge; Paula Schomberg; Per-Ulf Tunn; Thomas Kühne; Heribert Jürgens; Henk van den Berg; Tom Böhling; Susan Picton; Marleen Renard; Peter Reichardt; Joachim Gerss; Trude Butterfass-Bahloul; Carol Morris; Pancras C. W. Hogendoorn; Beatrice Seddon; Gabriele Calaminus; Maria Michelagnoli; Catharina Dhooge; Matthew R. Sydes; Mark Bernstein

doi:10.1200/JCO.2014.60.0734

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

Stefan S. Bielack
, Sigbjørn Smeland
, Jeremy S. Whelan
, Neyssa Marina
, Gordana Jovic
, Jane M. Hook
, Mark D. Krailo
, Mark Gebhardt
, Zsuzsanna Pápai
, James Meyer
, Helen Nadel
, R. Lor Randall
, Claudia Deffenbaugh
, Rajaram Nagarajan
, Bernadette Brennan
, G. Douglas Letson
, Lisa A. Teot
, Allen Goorin
, Daniel Baumhoer
, Leo Kager

Mathias Werner, Ching C. Lau, Kirsten Sundby Hall, Hans Gelderblom, Paul Meyers, Richard Gorlick, Reinhard Windhager, Knut Helmke, Mikael Eriksson, Peter M. Hoogerbrugge, Paula Schomberg, Per-Ulf Tunn, Thomas Kühne, Heribert Jürgens, Henk van den Berg, Tom Böhling, Susan Picton, Marleen Renard, Peter Reichardt, Joachim Gerss, Trude Butterfass-Bahloul, Carol Morris, Pancras C. W. Hogendoorn, Beatrice Seddon, Gabriele Calaminus, Maria Michelagnoli, Catharina Dhooge, Matthew R. Sydes, Mark Bernstein

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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 mu g/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 started IFN-alpha-2b or stopped prematurely. Long-term follow-up for events and survival continues. (C) 2015 American Society of Clinical Oncology

Original language	English
Pages (from-to)	2279-U92
Journal	Journal of clinical oncology
Volume	33
Issue number	20
DOIs	https://doi.org/10.1200/JCO.2014.60.0734
Publication status	Published - 2015

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Bielack, S. S., Smeland, S., Whelan, J. S., Marina, N., Jovic, G., Hook, J. M., Krailo, M. D., Gebhardt, M., Pápai, Z., Meyer, J., Nadel, H., Randall, R. L., Deffenbaugh, C., Nagarajan, R., Brennan, B., Letson, G. D., Teot, L. A., Goorin, A., Baumhoer, D., ... Bernstein, M. (2015). 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. Journal of clinical oncology, 33(20), 2279-U92. https://doi.org/10.1200/JCO.2014.60.0734

Bielack, Stefan S. ; Smeland, Sigbjørn ; Whelan, Jeremy S. et al. / 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. In: Journal of clinical oncology. 2015 ; Vol. 33, No. 20. pp. 2279-U92.

@article{cc701b3746024bc88d77e67ea8fdcab3,

title = "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",

abstract = "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 mu g/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 started IFN-alpha-2b or stopped prematurely. Long-term follow-up for events and survival continues. (C) 2015 American Society of Clinical Oncology",

author = "Bielack, \{Stefan S.\} and Sigbj{\o}rn Smeland and Whelan, \{Jeremy S.\} and Neyssa Marina and Gordana Jovic and Hook, \{Jane M.\} and Krailo, \{Mark D.\} and Mark Gebhardt and Zsuzsanna P{\'a}pai and James Meyer and Helen Nadel and Randall, \{R. Lor\} and Claudia Deffenbaugh and Rajaram Nagarajan and Bernadette Brennan and Letson, \{G. Douglas\} and Teot, \{Lisa A.\} and Allen Goorin and Daniel Baumhoer and Leo Kager and Mathias Werner and Lau, \{Ching C.\} and \{Sundby Hall\}, Kirsten and Hans Gelderblom and Paul Meyers and Richard Gorlick and Reinhard Windhager and Knut Helmke and Mikael Eriksson and Hoogerbrugge, \{Peter M.\} and Paula Schomberg and Per-Ulf Tunn and Thomas K{\"u}hne and Heribert J{\"u}rgens and \{van den Berg\}, Henk and Tom B{\"o}hling and Susan Picton and Marleen Renard and Peter Reichardt and Joachim Gerss and Trude Butterfass-Bahloul and Carol Morris and Hogendoorn, \{Pancras C. W.\} and Beatrice Seddon and Gabriele Calaminus and Maria Michelagnoli and Catharina Dhooge and Sydes, \{Matthew R.\} and Mark Bernstein",

year = "2015",

doi = "10.1200/JCO.2014.60.0734",

language = "English",

volume = "33",

pages = "2279--U92",

journal = "Journal of clinical oncology",

issn = "0732-183X",

publisher = "American Society of Clinical Oncology",

number = "20",

}

Bielack, SS, Smeland, S, Whelan, JS, Marina, N, Jovic, G, Hook, JM, Krailo, MD, Gebhardt, M, Pápai, Z, Meyer, J, Nadel, H, Randall, RL, Deffenbaugh, C, Nagarajan, R, Brennan, B, Letson, GD, Teot, LA, Goorin, A, Baumhoer, D, Kager, L, Werner, M, Lau, CC, Sundby Hall, K, Gelderblom, H, Meyers, P, Gorlick, R, Windhager, R, Helmke, K, Eriksson, M, Hoogerbrugge, PM, Schomberg, P, Tunn, P-U, Kühne, T, Jürgens, H, van den Berg, H, Böhling, T, Picton, S, Renard, M, Reichardt, P, Gerss, J, Butterfass-Bahloul, T, Morris, C, Hogendoorn, PCW, Seddon, B, Calaminus, G, Michelagnoli, M, Dhooge, C, Sydes, MR & Bernstein, M 2015, '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', Journal of clinical oncology, vol. 33, no. 20, pp. 2279-U92. https://doi.org/10.1200/JCO.2014.60.0734

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. / Bielack, Stefan S.; Smeland, Sigbjørn; Whelan, Jeremy S. et al.
In: Journal of clinical oncology, Vol. 33, No. 20, 2015, p. 2279-U92.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - 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

AU - Bielack, Stefan S.

AU - Smeland, Sigbjørn

AU - Whelan, Jeremy S.

AU - Marina, Neyssa

AU - Jovic, Gordana

AU - Hook, Jane M.

AU - Krailo, Mark D.

AU - Gebhardt, Mark

AU - Pápai, Zsuzsanna

AU - Meyer, James

AU - Nadel, Helen

AU - Randall, R. Lor

AU - Deffenbaugh, Claudia

AU - Nagarajan, Rajaram

AU - Brennan, Bernadette

AU - Letson, G. Douglas

AU - Teot, Lisa A.

AU - Goorin, Allen

AU - Baumhoer, Daniel

AU - Kager, Leo

AU - Werner, Mathias

AU - Lau, Ching C.

AU - Sundby Hall, Kirsten

AU - Gelderblom, Hans

AU - Meyers, Paul

AU - Gorlick, Richard

AU - Windhager, Reinhard

AU - Helmke, Knut

AU - Eriksson, Mikael

AU - Hoogerbrugge, Peter M.

AU - Schomberg, Paula

AU - Tunn, Per-Ulf

AU - Kühne, Thomas

AU - Jürgens, Heribert

AU - van den Berg, Henk

AU - Böhling, Tom

AU - Picton, Susan

AU - Renard, Marleen

AU - Reichardt, Peter

AU - Gerss, Joachim

AU - Butterfass-Bahloul, Trude

AU - Morris, Carol

AU - Hogendoorn, Pancras C. W.

AU - Seddon, Beatrice

AU - Calaminus, Gabriele

AU - Michelagnoli, Maria

AU - Dhooge, Catharina

AU - Sydes, Matthew R.

AU - Bernstein, Mark

PY - 2015

Y1 - 2015

N2 - 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 mu g/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 started IFN-alpha-2b or stopped prematurely. Long-term follow-up for events and survival continues. (C) 2015 American Society of Clinical Oncology

AB - 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 mu g/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 started IFN-alpha-2b or stopped prematurely. Long-term follow-up for events and survival continues. (C) 2015 American Society of Clinical Oncology

U2 - 10.1200/JCO.2014.60.0734

DO - 10.1200/JCO.2014.60.0734

M3 - Article

C2 - 26033801

SN - 0732-183X

VL - 33

SP - 2279-U92

JO - Journal of clinical oncology

JF - Journal of clinical oncology

IS - 20

ER -

Bielack SS, Smeland S, Whelan JS, Marina N, Jovic G, Hook JM et al. 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. Journal of clinical oncology. 2015;33(20):2279-U92. doi: 10.1200/JCO.2014.60.0734