High-Dose Treosulfan and Melphalan as Consolidation Therapy Versus Standard Therapy for High-Risk (Metastatic) Ewing Sarcoma

• DOI: 10.1200/jco.21.01942
• Publication Date: 2022-04-15T19:59:15Z
• Authors: Raphael Koch; Hans Gelderblom; Lianne Haveman; Benedicte Brichard; Heribert Jürgens; Sona Cyprova; Henk van den Berg; Wolf Hassenpflug; Anna Raciborska; Torben Ek; Daniel Baumhoer; Gerlinde Egerer; Hans Theodor Eich; Marleen Renard; Peter Hauser; Stefan Burdach; Judith Bovee; Fiona Bonar; Peter Reichardt; Jarmila Kruseova; Jendrik Hardes; Thomas Kühne; Torsten Kessler; Stephane Collaud; Marie Bernkopf; Trude Butterfaß-B...; Catharina Dhooge; Sebastian Bauer; János Kiss; Michael Paulussen; Angela Hong; Andreas Ranft; Beate Timmermann; Jelena Rascon; Volker Vieth; Jukka Kanerva; Andreas Faldum; Markus Metzler; Wolfgang Hartmann; Lars Hjorth; Vivek Bhadri; Uta Dirksen
• Keywords: Melphalan; Treosulfan

Ewing 2008R3 was conducted in 12 countries and evaluated the effect of treosulfan melphalan high-dose chemotherapy (TreoMel-HDT) followed by reinfusion autologous hematopoietic stem cells on event-free survival (EFS) overall high-risk sarcoma (EWS).Phase III, open-label, prospective, multicenter, randomized controlled clinical trial. Eligible patients had disseminated EWS with metastases to bone and/or other sites, excluding only pulmonary metastases. Patients received six cycles vincristine, ifosfamide, doxorubicin, etoposide induction eight actinomycin D, cyclophosphamide consolidation therapy. were randomly assigned receive additional TreoMel-HDT or no further treatment (control). The random assignment stratified number (1, 2-5, > 5). one-sided adaptive-inverse-normal-4-stage-design changed after first interim analysis via Müller-Schäfer method.Between 2009 2018, 109 assigned, 55 TreoMel-HDT. With a median follow-up 3.3 years, there significant difference EFS between control adaptive design (hazard ratio [HR] 0.85; 95% CI, 0.55 1.32, intention-to-treat). Three-year 20.9% (95% 11.5 37.9) 19.2% 10.8 34.4) patients. results similar per-protocol collective. Males treated better compared controls: 1.0 years 0.8 2.2) versus 0.6 0.5 0.9); P = .035; HR 0.52 (0.28 0.97). age < 14 benefited from 3-years 39.3% 20.4 75.8%) 9% 2.4 34); .016; 0.40 (0.19 0.87). These effects This observation is supported comparable nonrandomized trial EE99R3.In very EWS, benefit for entire cohort may be children years.