Phase 2 trial of irinotecan-temozolomide with or without dasatinib-rapamycin for relapsed or refractory neuroblastoma

The randomized phase 2 RIST-rNB-2011 trial, in 40 centers in Germany and Austria, compared irinotecan-temozolomide plus dasatinib-rapamycin (RIST regimen) versus irinotecan-temozolomide (control) for relapsed or refractory neuroblastoma (R/R NB). The RIST group included 60 patients and the control group included 63 patients. The median progression-free survival (primary endpoint) was 11 months with RIST versus 5 months with control (HR 0.62; p=0.019), whereas the median overall survival was 20 months with RIST versus 16 months with control (HR 0.68; p=0.073). Among the 48 patients with amplified MYCN the median PFS was 6 months with RIST versus 2 months with control (HR 0.45; p=0.012) whereas among the patients without amplified MYCN the median PFS was 14 months with RIST versus 8 months with control (HR 0.84; p=0.49). The most common adverse events were neutropenia (81% with RIST versus 82% with control), thrombocytopenia (76% versus 68%), and anemia (58% versus 63%). One patient in the RIST group died of treatment-related multiorgan failure. The authors conclude that among patients with R/R NB, addition of dasatinib-rapamycin to irinotecan-temozolomide improved PFS and OS; this improvement was limited to MYCN-amplified neuroblastoma.