A randomized phase II trial (Children’s Oncology Group [COG] ANBL1221) has resulted in the selection of dinutuximab (Unituxin) plus irinotecan/temozolomide as a regimen to be further evaluated in the treatment of pediatric patients with refractory or relapsed neuroblastoma. Study results were reported by Mody et al in The Lancet Oncology.
In the open-label selection design trial, 35 evaluable patients from 27 COG member institutions were randomized between February 2013 and March 2015 to receive dinutuximab (n = 17) or temsirolimus (Torisel; n = 18) in addition to irinotecan/temozolomide. Patients in both groups received oral temozolomide (100 mg/m² per dose) and intravenous irinotecan (50 mg/m² per dose) on days 1 to 5 of 21-day cycles. Intravenous temsirolimus was given at 35 mg/m² per dose on days 1 and 8; intravenous dinutuximab was given at 25 mg/m²/d or (after manufacturing change and dosing revision) 17.5 mg/m²/d on days 2 to 5, along with granulocyte macrophage colony-stimulating factor on days 6 to 12.
The primary endpoint was objective response on central review after six cycles of treatment. The median age was 4.7 years in the dinutuximab group and 7.0 years in the temsirolimus group.
Response Rates and Toxicity
Response was observed in nine patients (53%) in the dinutuximab group, including a complete response in five, compared with one patient (6%; one partial response) in the temsirolimus group. Stable disease was observed in an additional 24% vs 56% of patients, respectively.
The most common grade ≥ 3 adverse events were pain (44%), hypokalemia (38%), neutropenia (25%), thrombocytopenia (25%), anemia (25%), fever and infection (25%), and hypoxia (25%) in the dinutuximab group and neutropenia (44%), anemia (33%), thrombocytopenia (28%), increased alanine transaminase (28%), and hypokalemia (22%) in the temsirolimus group. No deaths related to study therapy were observed.
The investigators concluded: “Irinotecan-temozolomide-dinutuximab met protocol-defined criteria for selection as the combination meriting further study, whereas irinotecan-temozolomide-temsirolimus did not. Irinotecan-temozolomide-dinutuximab shows notable anti-tumour activity in patients with relapsed or refractory neuroblastoma. Further evaluation of biomarkers in a larger cohort of patients might identify those most likely to respond to this chemoimmunotherapeutic regimen.”
The study was funded by the National Cancer Institute.
Rochelle Bagatell, MD, of Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, is the corresponding author of The Lancet Oncology article.
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