EWING 2008 Results Summary
The EWING 2008 (EE08) was a joint study of the European and North American Ewing sarcoma study groups.
The study was aimed at optimising treatment and treatment outcomes for patients with newly diagnosed Ewing sarcoma. It was open to all patients diagnosed with Ewing sarcoma, localised or metastatic (spread to other parts of the body), who were considered eligible for preoperative combination chemotherapy.
All patients enrolled received initial chemotherapy consisting of six cycles of four-drug combination (vincristine, ifosfamide, doxorubicin and etoposide – known as VIDE). The decision regarding local therapy was made following the fifth cycle, with a preference for surgery with or without radiotherapy.
A total of 35 patients were recruited from nine Australia and New Zealand hospitals (sites).
Groups and results summary
Standard Risk (R1): In this group, patients were randomly allocated to different groups to examine whether add-on treatment with another drug (zoledronic acid), in addition to induction and maintenance chemotherapy, improves event-free survival in patients had a good response to first-line chemotherapy. Patients were considered to have a “good response” if at surgery, their original tumour was found to have less than 10% viable cells – meaning that less than 10% of the original tumour was still alive and also did not spread to other parts of the body.
- Result – The arm R1 cohort experimental design showed that the addition of another drug (zoledronic acid) was of no benefit. Therefore, this was safely removed from treatment regimens for these patients.
High Risk (R2): In a randomised trial to examine whether high-dose chemotherapy using busulfan-melphalan with autologous stem cell reinfusion (meaning that patients received their own cells), compared with standard chemotherapy, improves event-free survival in patients who did not respond as well to first-line chemotherapy (R2loc), as with patients with lung metastases (R2pulm).
- Result – The arm R2 cohort of patients showed that:
- Patients with localised disease: high-dose chemotherapy improved survival outcomes compared to standard chemotherapy with cyclophosphamide (VAI).
- Patients that had lung metastatic tumours had no clear benefit from high-dose chemotherapy compared with conventional chemotherapy with VAI and whole lung irradiation. Therefore, these patients will not be subjected to high-dose chemo regimens.
Very High Risk (R3): Patients in this group had tumours spread throughout the body beyond just the lung, such as to the bone and/or other body parts.
- Result – High-dose chemotherapy (treosulfan-melphalan, TreoMel) seems to be of benefit for children aged below 14 years old. However, there was no benefit of additional high-dose chemotherapy with TreoMel compared to standard chemotherapy for patients older than 14 years old.
The results from this important EE08 study will dictate how Ewing sarcoma patients are treated going forward and to improve treatment outcomes.
The findings are being incorporated into the next iteration of this work for the INTER-EWING study that is currently being developed with our collaborators, the children’s cancer cooperative group, ANZCHOG.
The study is being submitted for grant funding to Canteen via the MRFF scheme.
Firstly and foremost, ANZSA is grateful to the patients and families who participated in this study. ANZSA thanks and acknowledges all the EE08 local and international partners, investigators and sites. ANZSA is also grateful for the support of the Rainbows for Kate Foundation for funding this study and their ongoing support of ANZSA and sarcoma research.
For more info about EE08, please visit anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12616001524482
Publications
- Whelan J et al. Euro-E.W.I.N.G.99 and EWING-2008 Investigators. High-Dose Chemotherapy and Blood Autologous Stem-Cell Rescue Compared With Standard Chemotherapy in Localized High-Risk Ewing Sarcoma: Results of Euro-E.W.I.N.G.99 and Ewing-2008. J Clin Oncol. 2018 Sep 6;36(31)
- Dirksen U et al. High-dose chemotherapy compared with standard chemotherapy and lung radiation in Ewing sarcoma with pulmonary metastases: results of the European Ewing tumour working initiative of national groups, 99 trial and EWING 2008. J Clin Oncol. 2019; 37:3192-3202
- Efficacy of add-on treosulfan and melphalan high-dose therapy in patients with high-risk metastatic Ewing sarcoma: Report from the International Ewing 2008R3 trial. J Clin Oncol 38: 2020 (suppl; abstr 11501)
- Efficacy of maintenance therapy with zoledronic acid in patients with localised Ewing sarcoma: Report from the international Ewing 2008 trial. J Clin Oncol 38: 2020 (suppl; abstr 11523)