Phase II study of alisertib as a single agent for treating recurrent or progressive atypical teratoid/rhabdoid tumor. Issue 2 (2nd June 2022)

• Record Type: Journal Article
• Authors: Upadhyaya, Santhosh A; Campagne, Olivia; Billups, Catherine A; Orr, Brent A; Onar-Thomas, Arzu; Tatevossian, Ruth G; Mostafavi, Roya; Myers, Jason R; Vinitsky, Anna; Moreira, Daniel C; Lindsay, Holly B; Kilburn, Lindsay; Baxter, Patricia; Smith, Amy; Crawford, John R; Partap, Sonia; Bendel, Anne E; Aguilera, Dolly G; Nichols, Kim E; Rampersaud, Evadnie; Ellison, David W; Klimo, Paul; Patay, Zoltan; Robinson, Giles W; Broniscer, Alberto; Stewart, Clinton F; Wetmore, Cynthia; Gajjar, Amar
• Is Part Of: Neuro-oncology. Volume 25:Issue 2(2023)
• Page Start: 386
• Page End: 397
• Publication Date: 2022-06-02
• Subjects: alisertib -- alisertib pharmacokinetics -- atypical teratoid/rhabdoid tumor -- Aurora kinase A; Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noac151
• Languages: English
• ISSNs: 1522-8517

Abstract

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 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 (Cmax ) of 10.1 ± 3.0 µM and faster time to Cmax (Tmax = 1.2 ± 0.7 h) than those who received tablets (Cmax = 5.7 ± 2.4 µM, Tmax = 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.