London WB, et al. - This study was designed to assess the historical time to disease progression and progression-free survival in patients with recurrent/refractory neuroblastoma treated in the modern era on Children's Oncology Group (COG) early-phase trials. This recent COG cohort of patients with recurrent/refractory neuroblastoma was inclusive and representative. In this first meta-analysis of progression-free survival (PFS), overall survival (OS), and time to disease progression (TTP) within the context of modern therapy, outcomes would inform the design of future phase 2 studies by providing a) historical context during the search for more effective agents; and, b) factors prognostic of PFS and OS after disease recurrence to stratify randomization.

Methods

• Experts investigated the first early-phase COG trial enrollment (sequential) of 383 distinct patients with recurrent/refractory neuroblastoma on 23 phase 1, 3 phase 1/2, and 9 phase 2 trials (August 2002 to January 2014) for progression-free survival (PFS), overall survival (OS), and time to disease progression (TTP).
• Moreover, planned frontline therapy for patients with high-risk neuroblastoma included hematopoietic stem cell transplantation (approximately two-thirds of patients underwent ≥1 hematopoietic stem cell transplantation); 13.2% of patients received dinutuximab.

Results

• The 1-year and 4-year PFS rates (±standard error) were 21%±2% and 6%±1%, respectively, whereas the 1-year and 4-year OS rates were 57%±3% and 20%±2%, respectively, from the time of the patient's first early-phase trial enrollment (383 patients).
• The median TTP was 58 days (interquartile range, 31-183 days [350 patients]).
• In addition, the median follow-up was 25.3 months (33 patients were found to be without disease recurrence/progression).
• As per observations, the median time from diagnosis to first disease recurrence/progression was 18.7 months (range, 1.4-64.8 months) (176 patients).
• Results highlighted MYCN amplification and 11q loss of heterozygosity as prognostic of worse PFS and OS (P=.003 and P<.0001, respectively, and P=.02 and P=.03, respectively) after early-phase trial enrollment.