Phase 2 trial of veliparib, local irradiation, and temozolomide in patients with newly diagnosed high-grade glioma: A Children’s Oncology Group study Journal Article

   

Authors:	Karajannis, M. A.; Onar-Thomas, A.; Lin, T.; Baxter, P. A.; Boué, D. R.; Cole, B. L.; Fuller, C.; Haque, S.; Jabado, N.; Lucas, J. T. Jr; MacDonald, S. M.; Matsushima, C.; Patel, N.; Pierson, C. R.; Souweidane, M. M.; Thomas, D. L.; Walsh, M. F.; Zaky, W.; Leary, S. E. S.; Gajjar, A.; Fouladi, M.; Cohen, K. J.
Article Title:	Phase 2 trial of veliparib, local irradiation, and temozolomide in patients with newly diagnosed high-grade glioma: A Children’s Oncology Group study
Abstract:	Background. The outcome for pediatric patients with high-grade glioma (HGG) remains poor. Veliparib, a potent oral poly(adenosine diphosphate-ribose) polymerase (PARP) 1/2 inhibitor, enhances the activity of radiotherapy and DNA-damaging chemotherapy. Methods. We conducted a single-arm, non-randomized phase 2 clinical trial to determine whether treatment with veliparib and radiotherapy, followed by veliparib and temozolomide, improves progression-free survival in pediatric patients with newly diagnosed HGG without H3 K27M or BRAF mutations, compared to patient-level data from historical cohorts with closely matching clinical and molecular features. Following surgical resection, newly diagnosed children with non-metastatic HGG were screened by rapid central pathology review and molecular testing. Eligible patients were enrolled on Stratum 1 (IDH wild-type) or Stratum 2 (IDH mutant). Results. Both strata were closed to accrual for futility after planned interim analyses. Among the 23 eligible patients who enrolled on Stratum 1 and received protocol therapy, the 1-year event-free survival (EFS) was 23% (standard error, SE = 9%) and the 1-year overall survival (OS) was 64% (SE = 10%). Among the 14 eligible patients who enrolled on Stratum 2 and received protocol therapy, the 1-year EFS was 57% (SE = 13%) and 1-year OS was 93% (SE = 0.7%). Conclusions. Rapid central pathology review and molecular testing for eligibility were feasible. The protocol therapy including radiation, veliparib, and temozolomide was well tolerated but failed to improve outcomes compared to clinically and molecularly matched historical control cohorts treated with higher doses of alkylator chemotherapy. © The Author(s) 2024.
Keywords:	adolescent; child; preschool child; child, preschool; survival rate; clinical trial; temozolomide; brain tumor; follow up; glioma; brain neoplasms; follow-up studies; antineoplastic agent; cancer grading; phase 2 clinical trial; antineoplastic combined chemotherapy protocols; pathology; glioblastoma; therapy; benzimidazole derivative; benzimidazoles; chemoradiotherapy; high-grade glioma; veliparib; neoplasm grading; humans; prognosis; human; male; female
Journal Title:	Neuro-Oncology
Volume:	27
Issue:	4
ISSN:	1522-8517
Publisher:	Oxford University Press
Date Published:	2025-04-01
Start Page:	1092
End Page:	1101
Language:	English
DOI:	10.1093/neuonc/noae247
PUBMED:	39560182
PROVIDER:	scopus
PMCID:	PMC12083075
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-105005523389&doi=10.1093%2fneuonc%2fnoae247&partnerID=40&md5=41aa77b13add7c89540ff3971a2fb37f
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Matthias Karajannis -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/225517