Juliet C. Gray, Rebekah Weston, Cormac Owens, Adela Cañete, Marion Gambart, Bram De Wilde, Karsten Nysom, Natasha K. A. van Eijkelenburg, Ruth Ladenstein, Aurora Castellano, Nicolas U. Gerber, Lynley V. Marshall, Giuseppe Barone, Alba Rubio‐San‐Simón, Antony Ng, Sucheta Vaidya, Soledad Gallego, Guy Makin, G.A. Amos Burke, Anthony McCarthy, Dermot Murphy, C. Michel Zwaan, Ricardo López Almaraz, Sarah Jannier, Estelle Thébaud, Nadège Corradini, Dan Yeomanson, Lisa Howell, Deborah A. Tweddle, Martin Elliott, Dave Hobin, Dominique Valteau‐Couanet, Gudrun Schleiermacher, Pascal Chastagner, Anne Sophie Defachelles, Bénédicte Brichard, Sally L. George, Louis Chesler, Jennifer Laidler, Charlotte Firth, Grace Holt, V. V. Moroz, Andrew D.J. Pearson, Simon Gates, Keith Wheatley, Pamela Kearns, Lucas Moreno
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.