Abstract
Background
Recurrent atypical teratoid/rhabdoid tumor (AT/RT) is, most often, a fatal pediatric malignancy with limited curative options.
Methods
We conducted a phase II study of Aurora kinase A inhibitor alisertib in patients aged <22 years with recurrent AT/RT. Patients received alisertib once daily (80 mg/m
2 as enteric-coated tablets or 60 mg/m
2 as liquid formulation) on Days 1–7 of a 21-day cycle until progressive disease (PD) occurred. Alisertib plasma concentrations were measured in cycle 1 on Days 1 (single dose) and 7 (steady state) and analyzed with noncompartmental pharmacokinetics. Trial efficacy end point was ≥10 participants with stable disease (SD) or better at 12 weeks.
Results
SD (n=8) and partial response (PR) (n=1) were observed among 30 evaluable patients. Progression-free survival (PFS) was 30.0% ± 7.9% at 6 months and 13.3% ± 5.6% at 1 year. One-year overa ll survival (OS) was 36.7% ± 8.4%. Two patients continued treatment for >12 months. PFS did not differ by AT/RT molecular groups. Neutropenia was the most common adverse effect (n=23/30, 77%). The 22 patients who received liquid formulation had a higher mean maximum concentration (C
max) of 10.1 ± 3.0 µM and faster time to C
max (T
max = 1.2 ± 0.7 h) than those who received tablets (C
max = 5.7 ± 2.4 µM, T
max = 3.4 ± 1.4 h).
Conclusions
Although the study did not meet pre-determined efficacy end point, single agent alisertib was well tolerated by children with recurrent AT/RT, and SD or PR was observed in approximately a third of the patients.
