OBJECTIVES: Anti-GD2 chemoimmunotherapy is becoming therapy of choice in relapse/refractory neuroblastoma. A randomized controlled trial of dinutuximab beta with chemotherapy versus chemotherapy alone in this setting met the success criteria, but comparison of larger cohorts treated with historical treatment modalities is warranted to inform clinical practice and further research.

METHODS: Studies of dinutuximab beta combined with chemotherapy and of chemotherapy alone enrolling both relapsed and refractory patients were identified in a systematic literature review using PubMed and EMBASE. Prospective and retrospective studies published or presented at conferences from 2000 in patients treated with temozolomide plus irinotecan (TEMIRI), temozolomide plus topotecan (TOTEM), cyclophosphamide plus topotecan, with and without dinutuximab beta and with and without bevacizumab, were included. Guyot 2012 algorithm and Digitizelt software were used for digitization of Progression Free Survival (PFS) Kaplan-Meier curves with approximated individual patient data pooled for analyses using log-rank test and Cox proportional hazards model with no adjustments. Objective response rates (ORR) measured as best response were compared using relative risk (RR) and odds ratio (OR).

RESULTS: Data from 636 patients from 15 studies (17 arms, three from randomized controlled trials) were included in the analyses. Dinutuximab beta with chemotherapy improved PFS versus pooled TOTEM or TEMIRI chemotherapy (HR=0.58 [95%CI: 0.39-0.86], p=0.007), versus all chemotherapy without bevacizumab (HR=0.55 [0.39-0.79], p=0.001), and versus all chemotherapy with or without bevacizumab (HR=0.59 [0.42-0.85], p=0.004). Respective RR were: 3.02 [2.01-4.53], p<0.001; 2.60 [1.95-3.46], p<0.001; 2.54 [1.93-3.33], p<0.001, and respective OR were 4.99 [2.77-9.00], p<0.001; 4.16 [2.56-6.74], p<0.001; 4.04 [2.52-6.46], p<0.001.

CONCLUSIONS: Our results demonstrate improved objective response and progression free survival outcomes with dinutuximab beta chemoimmunotherapy in relapsed/refractory neuroblastoma and support recommendations for its use in this setting. Analysis with individual patient data adjusted for predictors of outcomes would allow for a more precise estimate of treatment effect.