Dinutuximab Beta Added to Temozolomide-Based Chemotherapy for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON Immuno Phase II Trial
Abstract
PURPOSE Outcomes 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 METHODS Patients 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/m 2 /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. RESULTS Sixty-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. CONCLUSION Within a randomized phase II setting, results observed with addition of dB to T-based chemotherapy in RR-HR-NB warrant further evaluation.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (47)
Juliet C. Gray
Centre for Cancer Immunology, University of Southampton, Southampton, United Kingdom
Rebekah Weston
Juliet Gray, PhD, FRCPCH, Centre for Cancer Immunology, University of Southampton, Southampton, United Kingdom; Rebekah Weston, PhD, FRCPCH, and Simon Gates, PhD, DIC, FHEA, Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham, Birmingham, United Kingdom; and Lucas Moreno, MD, PhD, Hospital Vall d'Hebron, Barcelona, Spain
Cormac Owens
Our Lady's Children's Hospital, Dublin, Republic of Ireland
Adela Canete
Unidad de Oncologia Pediatrica, Institute de Investigación Sanitaria La Fe, Valencia, Spain
Marion Gambart
Hôpital des Enfants, Toulouse, France
Bram de Wilde
Karsten Nysom
Natasha van Eijkelenburg
Princess Máxima Centre for Paediatric Oncology, Utrecht, The Netherlands
Ruth Ladenstein
St Anna Children's Cancer Research Institute CCRI, Vienna, Austria
Aurora Castellano
IRCCS Ospedale Pediatrico Bambino Gesu, Rome, Italy
Nicolas U. Gerber
Department of Oncology, University Children's Hospital, Zürich, Switzerland
Lynley V. Marshall
Children & Young People's Unit, The Royal Marsden NHS Foundation Trust, London, United Kingdom
Giuseppe Barone
Great Ormond Street Hospital, London, United Kingdom
Alba Rubio-San-Simon
Antony Ng
Bristol Royal Hospital for Children, Bristol, United Kingdom
Sucheta Vaidya
The Royal Marsden Hospital, Institute of Cancer Research, London, United Kingdom
Soledad Gallego
Hospital Vall d'Hebron, Barcelona, Spain
Guy Makin
Royal Manchester Children's Hospital, Manchester, United Kingdom
G. A. Amos Burke
Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom
Anthony McCarthy
Royal Belfast Hospital for Sick Children, Belfast, United Kingdom
Dermot Murphy
Al Jalila Children's Speciality Hospital, Dubai, United Arab Emirates
C. Michel Zwaan
1Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Ricardo Lopez-Almaraz
Pediatric Oncology/Haematology Unit, Hospital Universitario Cruces & Biobizkaia Health Research Institute, Barakaldo, Spain
Sarah Jannier
Hôpital de Hautepierre, Strasbourg, France
Estelle Thebaud
Department of Pediatric Oncology, Centre Hospitalier Universitaire, Nantes, France
Nadege Corradini
Centre Léon Bérard, Department of Pediatric Oncology, Institut d'Hematologie et d'Oncologie Pédiatrique, Lyon, France
Dan Yeomanson
Sheffield Children's Hospital, Sheffield, United Kingdom
Lisa Howell
Alder Hey Children's Hospital, Liverpool, United Kingdom
Deborah A. Tweddle
Royal Victoria Infirmary Newcastle and Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
Martin Elliott
Leeds General Infirmary, Leeds, United Kingdom
Dave Hobin
Birmingham Women and Children's Hospital, Birmingham, United Kingdom
Dominique Valteau-Couanet
Gustave Roussy, Villejuif, France
Gudrun Schleiermacher
Institut Curie, Paris, France
Pascal Chastagner
10Pediatric Hematology Unit, University Hospital of Nancy, Nancy, France, Nancy, France
Anne Sophie Defachelles
Oscar Lambret Cancer Center, Department of Pediatric Oncology, Lille, France
Benedicte Brichard
53Department of Paediatric Haematology and Oncology, Cliniques Universitaires saint Luc, UClouvain, Brussels, Belgium, Brussels, Belgium
Sally George
The Royal Marsden Hospital, Institute of Cancer Research, London, United Kingdom
Louis Chesler
Jennifer Laidler
Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham, Birmingham, United Kingdom
Charlotte Firth
Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham, Birmingham, United Kingdom
Grace Holt
Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham, Birmingham, United Kingdom
Veronica Moroz
Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham, Birmingham, United Kingdom
Andrew D.J. Pearson
The Royal Marsden Hospital, Institute of Cancer Research, London, United Kingdom
Simon Gates
Juliet Gray, PhD, FRCPCH, Centre for Cancer Immunology, University of Southampton, Southampton, United Kingdom; Rebekah Weston, PhD, FRCPCH, and Simon Gates, PhD, DIC, FHEA, Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham, Birmingham, United Kingdom; and Lucas Moreno, MD, PhD, Hospital Vall d'Hebron, Barcelona, Spain
Keith Wheatley
Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham, Birmingham, United Kingdom
Pam Kearns
Lucas Moreno