The ANBL0532 trial also does not address the important question as to whether tandem high-dose chemotherapy with autologous stem cell transplant results in benefit for all-comers with high-risk neuroblastoma, because just over half of the eligible patients underwent randomization. Although characteristics of the entire cohort and the randomized cohort were similar with respect to age, stage, tumor histology, and MYCN status, there may be differences unrelated to widely accepted neuroblastoma risk variables. A separate but important challenge in interpretation of these results, as with any clinical trial results, is to understand the generalizability of findings to patient populations who may not be enrolling in trials. Previous work in pediatric oncology showed that trial enrollment correlated with race, age, and zip code, and it is difficult to know whether the results of the ANBL0532 trial are applicable to patient groups who may not be well represented.

An additional challenge is that even though a difference in event-free survival was detected between groups assigned to receive single versus tandem transplant, and a difference in overall survival was detected in a post hoc analysis of patients who received immunotherapy, no difference in overall survival was detected in the overall randomized cohort. Overall survival was evaluated as a secondary outcome but the trial was not powered to detect a difference in overall survival. Moreover, as noted by the authors, overall survival can be influenced by therapies delivered after relapse. This is particularly relevant in an era in which relapse therapies have been shown to induce responses, including periods of remission.

Remarks from Rochelle Bagatell, MD, from the University of Pennsylvania, Philadelphia, and Meredith S. Irwin, MD, from the Hospital for Sick Children in Toronto, are adapted and condensed from an editorial accompanying the study by Park et al. Dr. Bagatell is the vice chair of the Children’s Oncology Group Neuroblastoma Disease Committee. Dr. Irwin reported receiving personal fees from Bayer Canada outside the submitted work and is the vice chair of the Children’s Oncology Group Neuroblastoma Biology Committee. Neither Dr. Bagatell nor Dr. Irwin was involved in the design of the ANBL0532 trial or in the analysis of the results.