Tyrosine kinase inhibitors in children and adolescents with recurrent/refractory sarcomas.

Abstract

e22011 Background: Treatment of recurrent/refractory (RR) sarcomas is challenging and outcomes with chemotherapy remain poor. Tyrosine kinases are key signalling proteins involved in cell growth and metastasis. Multitargeted tyrosine kinase inhibitors (TKI) that inhibit these proteins have shown relevant preliminary implications regarding therapeutics in sarcoma. The aim of this study is to assess safety and outcome of treatment with TKI in children and adolescents with RR sarcomas treated in a single center and add real world evidence. Methods: Medical records of children with RR sarcomas treated with TKI between between Jan 2021 and Dec 2024 were retrospectively evaluated for safety and outcome. TKI was used with regulatory approval. Results: Twenty-three patients (18 male, 5 female) recieved TKI ( 20 in addition to chemotherapy) for RR sarcomas (13 osteosarcoma, 6 Ewing Sarcoma, 2 rhabdomyosarcoma, 1 epitheloid sarcoma,1 sclerosing epitheloid fibrosarcoma) as second (14) or further line (9) treatment. The median age at diagnosis and at time of TKI initiation were 14 (3-17) and 16 (11-20) years, respectively. Ten patient had metastasis at diagnosis, 11 other developed metastasis at recurrence.The TKI used were regorafenib (18), pazopanib (3) , sorafenib (2) , seven patients switched from one to other TKI. TKI were used for a median of 12 (1-44) months. Two patients progressed (at 1, 2 months), 18 patients had stable disease (SD) for a median of 12 (3-17) months, 1 had a partial resonse (PR) that continues for 40+ months. 2 have a continued complete response for12+ months. Two of these patients recieved only pazopanib, one with metastatic (lung) sclerosing epitheloid fibrosarcoma for 40+ months with PR, one with epitheloid sarcoma for 16 months with SD. From the start of TKI, 15 have died at a median of 15 (2-43)months, 8 are alive for a median of 22 (1-44) months. The 2 year overall survival (OS) and progression free survival from diagnosis was 72.3% and 21% , from initiation of TKI was 34% and 11.4 %. Age, line of treatment was not associated with PFS; patiens with Ewing sarcoma, Epitheloid sarcoma and sclerosing epitheloid fibrosarcoma had better PFS on univariate analysis. Most common side effects were nausea, diarrhoea, hand foot skin reactions which were managable with temporary dose reductions and hypothyroidism in a patient that needed medication, resolved totally when TKI were discontinued for 3 months and started again as it was reused. Conclusions: Our real-world data suggest that TKI may be effective in RR sarcomas with acceptable toxicities. Inclusion of TKIs in earlier lines of treatment and/or maintenance therapy could be questions for future research.