| Title: |
Dinutuximab beta added to temozolomide-based chemotherapy for children with relapsed and refractory neuroblastoma : results of the ITCC-SIOPEN BEACON Immuno Phase II Trial |
| Authors: |
Gray, Juliet C.; Weston, Rebekah; Owens, Cormac; Canete, Adela; Gambart, Marion; De Wilde, Bram; Nysom, Karsten; van Eijkelenburg, Natasha; Ladenstein, Ruth; Castellano, Aurora; Gerber, Nicolas U.; Marshall, Lynley V.; Barone, Giuseppe; Rubio-San-Simon, Alba; Ng, Antony; Vaidya, Sucheta; Gallego, Soledad; Makin, Guy; Burke, G. A. Amos; McCarthy, Anthony; Murphy, Dermot; Zwaan, C. Michel; López-Almaraz, Ricardo; Jannier, Sarah; Thebaud, Estelle; Corradini, Nadege; Yeomanson, Dan; Howell, Lisa; Tweddle, Deborah A.; Elliott, Martin; Hobin, Dave; Valteau-Couanet, Dominique; Schleiermacher, Gudrun; Chastagner, Pascal; Defachelles, Anne Sophie; Brichard, Benedicte; George, Sally; Chesler, Louis; Laidler, Jennifer; Firth, Charlotte; Holt, Grace; Moroz, Veronica; Pearson, Andrew D.J.; Gates, Simon; Wheatley, Keith; Kearns, Pam; Moreno, Lucas |
| Source: |
JOURNAL OF CLINICAL ONCOLOGY ; ISSN: 0732-183X ; ISSN: 1527-7755 |
| Publication Year: |
2026 |
| Collection: |
Ghent University Academic Bibliography |
| Subject Terms: |
Medicine and Health Sciences; CLASSIFICATION-SYSTEM; RISK; SURVIVAL; ANTIBODY |
| Description: |
PURPOSEOutcomes for children with relapsed and refractory high-risk neuroblastoma (RR-HR-NBL) remain dismal. Here, we investigate addition of the anti-GD2 monoclonal antibody, dinutuximab beta (dB), to temozolomide (T)-based chemotherapy.MATERIALS AND METHODSPatients with RR-HR-NBL were randomly assigned in a 1:2 ratio to receive chemotherapy alone or chemotherapy with dB, given concurrently as a 7-day infusion (10 mg/m2/24 h). The trial had a factorial design, with some patients also randomly assigned between chemotherapy regimens (T v T-topotecan [TTo]). Crossover to dB with To/cyclophosphamide was allowed for patients randomly assigned to chemotherapy alone with disease progression (PD). The primary outcome was best objective response (complete or partial) rate (overall response rate [ORR]) during six cycles of treatment. Progression-free (PFS), overall survival (OS), and safety were secondary outcomes.RESULTSSixty-five patients were randomly assigned to chemotherapy alone (3 T, 19 TTo) or with dB (6 dBT, 37 dBTTo). The median age was 4 years; 28 and 37 patients had refractory and relapsed diseases, respectively. Baseline characteristics were balanced between arms. The ORR was 30.2% (13 of 43) and 18.2% (4 of 22) in dB and non-dB arms, the median PFS was 11.1 months (95% CI, 4.3 to 15.5) for dB patients and 3.8 months (95% CI, 1.9 to 7.9) for non-dB patients, respectively. The median OS was 25.7 months (95% CI, 11.4 to not reached [NR]) for dB patients and 17.1 months (95% CI, 7.6 to 54.6) for non-dB patients (upper 95% CI, NR in dB arm). Thirteen of 22 patients in the non-dB arm crossed over to dB with cyclophosphamide/To because of PD. Neurotoxicity was more common in the dB arm (grade 1 and 2: 26% v 9%, grade 3: 2.3% v 4.5%), but other toxicities were similar.CONCLUSIONWithin a randomized phase II setting, results observed with addition of dB to T-based chemotherapy in RR-HR-NB warrant further evaluation. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://biblio.ugent.be/publication/01KJ3K3W8CZ8496GGYMP5W3BKX; https://biblio.ugent.be/publication/01KJ3K3W8CZ8496GGYMP5W3BKX/file/01KJCPPHJKYQDF5AWFMKWMV8JN |
| DOI: |
10.1200/jco-25-01868 |
| Availability: |
https://biblio.ugent.be/publication/01KJ3K3W8CZ8496GGYMP5W3BKX; https://hdl.handle.net/1854/LU-01KJ3K3W8CZ8496GGYMP5W3BKX; https://doi.org/10.1200/jco-25-01868; https://biblio.ugent.be/publication/01KJ3K3W8CZ8496GGYMP5W3BKX/file/01KJCPPHJKYQDF5AWFMKWMV8JN |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.8A9B426A |
| Database: |
BASE |