ATRT-18. ALISERTIB USED IN PEDIATRIC ATRT

Abstract

Abstract BACKGROUND Atypical rhabdoid tumor (ATRT) is a rare and aggressive primary CNS tumor caused by variants or deletions in the tumor suppressor gene SMARCB1 (aka INI 1). SMARCB1 targets Aurora A kinase (AURKA), an important oncoprotein of the cell cycle. AURKA dysregulation can lead to genomic instability through its oncogenic effects. Alisertib is a selective AURKA inhibitor that has been explored for treatment in various cancers, including pediatric malignancies. METHODS Retrospective chart review of five patients diagnosed with ATRT, treated with Alisertib, at Nicklaus Children’s Hospital from 2019 - 2024. RESULTS of the 5 patients; three were females and two males, with a median age at diagnosis of 2 years. Only one patient had a germline mutation while the rest had somatic mutations. Prior to starting Alisertib therapy, all five patients received chemotherapy per multiple protocols; four patients underwent focal radiation therapy, three patients underwent resection, and two patients underwent tandem autologous transplants. All five patients were treated solely with Alisertib, median dose of 60 mg/m2 PO daily. Two patients had reduced doses during therapy secondary to cytopenia. One patient completed therapy over 13 months with partial response based on imaging. One patient presented progression of disease while on therapy and for that reason treatment was stopped. Three patients continue treatment: two with only Alisertib, one using Avastin and Sirolimus concurrently. CONCLUSIONS Prognosis in patients with ATRT is usually poor given its aggressive nature and high rate of recurrence despite intervention. It is important to note that treatment of ATRT is highly individualized and typically involves a combination of therapeutic modalities. While Alisertib is one of the newest treatment options, there’s limited literature of clinical improvement in patients with ATRT using this treatment. Therefore, further research on novel treatment options is warranted for the future.