CTP-03. A Phase 2 study of alisertib in combination therapy for newly diagnosed Atypical Teratoid/Rhabdoid Tumor (AT/RT)- Results from SJATRT strata B and C
Year: 2025
Type: conference-abstract
Abstract: BACKGROUND Atypical teratoid/rhabdoid (AT/RT) is an aggressive pediatric brain tumor, prevalent in children < 3 years(Y) of age. Though treatment with surgery, radiation and chemotherapy has improved clinical outcome, the cure rate remains suboptimal. Molecularly, AT/RT demonstrates alterations in SMARCB1 and SMARCA4 and methylation profiles sub-classify AT/RTs into AT/RT-MYC(MYC), AT/RT-SHH(SHH) and AT/RT-TYR(TYR). METHODS We conducted a phase 2 study of Aurora Kinase A inhibitor, alisertib, in combination with chemotherapy and radiotherapy (RT) in newly diagnosed AT/RT (Stratum B [B1-M0 & B2-M+]: < 36 months; Stratum C [C1-M0 & C2-M+] - ≥ 36 months). Stratum B1 patients received focal RT at ≥12 months of age and patients on stratum C1 (23.4 Gy) and C2 (36 Gy) received post-operative CSI. RESULTS 71 evaluable patients were enrolled on strata B1 (n=30), B2 (n=17), C1(n=13) and C2 (n=11). For, B1 (SHH:18, TYR:7, MYC:3, NC:2) the 3Y PFS and OS were 30.0% and 56.7%. B2 (SHH:8, TYR:7, MYC:2) had a 3Y PFS and OS of 0 and 17.6% and was closed early at PI discretion due to lack of efficacy. Stratum C1 (SHH:4, TYR:2 & MYC:6, NA:1, NC:1) the 3Y PFS and OS were 84.6% & 100.0% and for C2 (SHH:6 and MYC:3, NC:2), 63.6% was the 3Y PFS and OS. SHH patients had better PFS (p=0.036) in C2 in comparison to MYC. Strata C1 and C2 did not reach target accrual. There were no unexpected toxicities, most common grade 3 toxicities were related to myelosuppression. CONCLUSION Combination of alisertib with chemotherapy and RT was well tolerated, however, it didn’t improve survival in newly diagnosed AT/RT. The study confirms, albeit in small numbers, prior results of a higher survival for M0 patients with post-operative CSI in ≥ 36-month-old (C1). The PFS in M+ ≥ 36-month-old patients (C2) was higher with CSI than previously reported. Molecular subclass was not associated with outcome except in SHH in C2.
Source: Neuro-Oncology
Authors: Aditi Bagchi, Santhosh A Upadhyaya, Sandeep Dhanda, Catherine Billups, Patricia Baxter, Anne Bendel, Dolly Aguillera, Lindsey Kilburn, John Crawford, Sonia Partap, Emily Hanzlik, Quynh Tran, Alex Breuer, Wenjie Qi, Congyu Lu, Anjali Singh, Miya Richardson, Eroica Soans, Paul Klimo, Xin Zhou, Arzu O Thomas, Brent Orr, Thomas Merchant, Giles W Robinson, Amar Gajjar
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416140986
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