Journal
NEURO-ONCOLOGY
Volume 25, Issue 2, Pages 386-397Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/neuonc/noac151
Keywords
alisertib; alisertib pharmacokinetics; atypical teratoid; rhabdoid tumor; Aurora kinase A
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This study examines the use of Aurora kinase A inhibitor alisertib in children with recurrent AT/RT. The results show that alisertib is well tolerated in children with recurrent AT/RT, and approximately one-third of the patients observed stable disease or partial response.
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 overall 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 mu M and faster time to C-max (T-max = 1.2 +/- 0.7 h) than those who received tablets (C-max = 5.7 +/- 2.4 mu M, T-max = 3.4 +/- 1.4 h). Conclusions Although the study did not meet predetermined 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.
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