Possibility of using the combination of everolimus/sorafenib medications in the treatment of children and adolescents with refractory osteosarcoma and Ewing sarcoma.

e23513 Background: Treatment outcomes for children and adolescents with refractory osteosarcoma and Ewing's sarcoma remain unsatisfactory. According to the results of various international pilot studies, the rate of progression-free survival (PFS) tends steadily to zero at a median follow-up of 6-8 months. Methods: From May 2018 to August 2023, 12 children and adolescents with refractory course of osteosarcoma (in 11) and Ewing sarcoma (in 1) were included in this pilot study. The ratio of male to female patients was 7:5. The mean age was 13.4 years (7 to 17 years). All patients received chemotherapy: doxorubicin, cisplatin, high-dose methotrexate, high-dose ifosfamide, gemcitabine and docetaxel. All children and adolescents showed disease progression after chemotherapy before inclusion in this pilot study. Sorafenib was administered orally at a starting dose of 150 mg/m2 (with the option to escalate to 200 mg/m2) every 12 h, and everolimus was administered orally at a starting dose of 2.5 mg/m2 (with the option to escalate to 5 mg/m2) once daily for 28-day courses until disease progression or unacceptable toxicities. The control points for assessing therapy efficacy were six-month and one-year progression-free survival. Results: The most common variant of toxicity of the therapy performed was skin erythema (100%), palm-podontal syndrome (9%), and oral mucositis (18%). Hematologic toxicity did not exceed grades 1-2 (100%). Partial response was achieved in 4 patients (3 with osteosarcoma, 1 with Ewing's sarcoma), and disease stabilization was achieved in 8 patients. One-year survival without disease progression was 36.2 ± 18.9%, six-month survival was 54%; the maximum survival rate was 54%. The maximum period before disease progression was 13.3 months, with a mean follow-up of 7.8 ± 1.6 months. Conclusions: The Everolimus/sorafenib combination has demonstrated efficacy and satisfactory tolerability as therapy for refractory osteosarcoma and Ewing's sarcoma in children and adolescents, but further follow-up studies are needed.