Time to disease progression in children with relapsed or refractory neuroblastoma treated with ABT-751: A report from the Children's Oncology Group (ANBL0621)
Background: ABT-751, an orally bioavailable sulfonamide binds the colchicine site of beta-tubulin and inhibits microtubule polymerizaton. Prior phase I studies established the recommended dose in children with solid tumors as 200mg/m2 PO daily×7 days every 21 days and subjects with neuroblastoma experienced prolonged stable disease. We conducted a phase 2 study (NCT00436852) in children and adolescents with progressive neuroblastoma to determine if ABT-751 prolonged the time to progression (TTP) compared to a hypothesized standard based on a historical control population. Procedure: Children and adolescents (n=91) with a median (range) age 7.7 (2.3-21.5) years and progressive neuroblastoma were enrolled and stratified by disease status into disease measureable by CT/MRI (n=47) or disease assessable by 123I-metaiodobenzylguanine scintigraphy (MIBG, n=44). Response was evaluated using RECIST for measureable disease and the Curie score for MIBG-avid disease. Results: ABT-751 was well tolerated. The objective response rate was 7%. The median TTP was 42 days (95% CI: 36, 56) in the measureable disease stratum and 45 days (95% CI: 42, 85) in the MIBG-avid disease stratum. TTP was similar to the historical control group (n=136, median TTP 42 days). For the combined strata (n=91), 1-year progression free survival (PFS) was 13±4% and overall survival (OS) was 48±5%. Conclusions: The low objective response rate and failure to prolong TTP indicate that ABT-751 is not sufficiently active to warrant further development for neuroblastoma. However, this trial demonstrates the utility of TTP as the primary endpoint in phase 2 trials in children and adolescents with neuroblastoma. Pediatr Blood Cancer 2014;61:990-996. © 2013 Wiley Periodicals, Inc.
Pediatric Blood and Cancer
Fox, E., Mosse', Y., Meany, H., Gurney, J., Khanna, G., Jackson, H., Gordon, G., Shusterman, S., Park, J., Cohn, S., Adamson, P., London, W., Maris, J., & Balis, F. (2014). Time to disease progression in children with relapsed or refractory neuroblastoma treated with ABT-751: A report from the Children's Oncology Group (ANBL0621). Pediatric Blood and Cancer, 61 (6), 990-996. https://doi.org/10.1002/pbc.24900