(P 453) ROLE OF SECOND-LINE TREATMENT IN EWING SARCOMAS WITH POOR PROGNOSIS AT DIAGNOSIS: EXPERIENCE OF A SPANISH REFERENCE CENTER.

Objective: Relapsed Ewing sarcoma comprises an aggressive disease with a 5-year overall survival rate of about 15%. Prognosis is poor, especially if relapse occurs within the first 2 years after diagnosis. The REECur trial is the first to address this issue, with high-dose Ifosfamide being the best treatment in the second line, resulting in a progression free survival (PFS) of 5.7 months (m (95% CI,3.8-7.0) and a median overall survival (OS) 16.8 months (95% CI, 11.1-25.8).
The aim of our study was to describe our experience with second-line treatment in a reference center, focusing on patients with worse prognosis at diagnosis (high volume, metastatic at debur, or less than 90% necrosis after neoadjuvant treatment).

Methods: Patients diagnosed with Ewing sarcoma were treated with VAC/IE schema (regimen consisting of two parts: 7 cycles of VDC (vincristine, doxorubicin, cyclophosphamide) alternating with 7 cycles of IE (ifosfamide and etoposide)). At relapse, there were treated with different approved schemas.
We retrospectively analyzed 28 patients with poor prognosis at diagnosis who were with different schemas in the second line: cyclophosphamide + topotecan (CT) (14), high dose ifosfamide (IfoHD)(4), gemcitabine plus docetaxel (GemDoc)(4), irinotecan plus temozolamide (TEMIRI) (4), carboplatin and etoposide (CE) (2) and retreatment with Ifosfamide and etoposide (IE) (1)
Descriptive analysis was done, and the response to second-line treatment was analyzed based on three different factors: volume at debut, metastatic setting, and response to neoadjuvant treatment.

Results: Twenty-eight patients (pts) with relapsed Ewing sarcoma were analyzed retrospectively. The median age at diagnosis was 25 years (14-50) with a predominance of male patients (17 vs 11). 51,7% (15pts) presented with metastatic disease at debut (15), predominantly lung metastasis (41,1%). The median volume of the localized tumor was over 600cc. The time-lapse between first line and recurrence was 16 m.
The median PFS and OS for each schema were as follows: TEMIRI PFS 16 m (2-29) OS 31m (17-45), CT PFS 10,6 (5-16) OS44m (22-65), GemDoc PFS 8,3 (4-12) OS 41 (18-64), IfoHD PFS 7,5 (0-20) OS 19 (3-36) and CE PFS 2 (0-3) OS 21,5 (0-42). However, the differences were not significant ( p=0,1)
In terms of metastatic debut, this patients had a shorter OS. However, the most effective schema was GemDoc (37m) followed by TEMIRI (35m). In patients with non-metastatic debut, CT showed better OS (60m).
In case of high volume at debut, again patients with a higher primary tumor volume had a worse prognosis, with an OS of 36 m (25-47) compared to 38m (22-54) in those with a lower volume. In this setting, CT showed better OS, than others (40m).
Analyzing the OS in patient who did not achieve necrosis over 90% (only surgical patients), CT showed the best OS (41m), and again, a difference was observed with a worse OS in this patients.

Conclusion: The debut of the disease is a prognostic factor in Ewing sarcoma: metastatic debut, high tumor volume, and necrosis under 90% after neoadjuvant treatment showed a lower OS. The worst context is metastatic debut.
The REECur study is the first to analyze different second-line treatments; however, no differences were observed in tumors with poor prognosis.
In our retrospective study, TEMIRI had the best PFS (16m), but CT has better OS 44m in patients with a poor prognosis.
Analyzing the different settings in these patients, excluding metastatic disease CT showed the best data.