Activity Of Front-Line Window Therapy With Temozolomide Plus Irinotecan In Patients With Primary Multifocal Ewing Sarcoma: Isg/Aieop Ew-2 Protocol.

10516 Background: The prognosis of patients with primary multifocal metastatic Ewing sarcoma (PMES) remains dismal. So far, combination with temozolomide and irinotecan (TEMIRI) was tested in patients with refractory or relapsed disease. This study evaluates the activity and the tolerability of TEMIRI as front-line treatment in PMES. Methods: In the study-period 2012-2018, a front-line window therapy with 2 courses TEMIRI (temozolomide 100 mg/sqm/day + irinotecan 50 mg/sqm/day for 5 days every three weeks) was introduced as amendment to the ISG/AIEOP EW-2 protocol ( EUDRACT#2009-011197-15, Vers. 1.02 ) for patients with PMES. Main objective was to test the activity of TEMIRI evaluated by RECIST 1.1 criteria, with centralized revision of the radiological response. Secondary objectives included assessment of the toxicity profile and clinical benefit of the combination. A two-step study design by Simon was planned. Results: Thirty-four patients were enrolled. Median age at diagnosis was 19 years (range 3-55); males/females ratio was 2.4. Primary axial tumour was present in 24 (70%). After TEMIRI, RECIST response was as follows: partial response -20 (59%), stable disease -11 (32%), progression disease -3 (9%). After TEMIRI, amelioration in ECOG/Lansky score was achieved in 25/34 (73,5%), and reduction or disappearance of pain was observed in 31/34 patients (91%). TEMIRI toxicity was manageable: incidence of grade 3-4 nonhaematological and haematological toxicity was 3% and 3%, respectively (67/68 evaluable courses). At the time of the present analysis, 11 patients are alive; 7 of them are in complete remission and completed their treatment program (5-drug standard chemotherapy). With a median follow-up of 31 months (range 23-75), the 3-year survival estimate is 36,5%±0.09. Conclusions: Upfront TEMIRI x 2 courses showed an encouraging activity, with response rate 59% and deserves further evaluation combined with conventional treatments also in non-metastatic patients. In PMES new treatment strategies are urgently needed. Clinical trial information: NCT02727387.