Dinutuximab plus granulocyte-macrophage colony-stimulating factor (GM-CSF) is not an effective treatment option for recurrent osteosarcoma, according to research published in the European Journal of Cancer.1

In a phase 2 trial, dinutuximab plus GM-CSF produced a low disease control rate (DCR) that did not meet a historical benchmark. 

The single-arm trial (ClinicalTrials.gov Identifier: NCT02484443) enrolled patients with recurrent pulmonary osteosarcoma in complete surgical remission. The 39 evaluable patients had a median age of 15 (range, 7 to 26) years. Most patients had nonmetastatic disease at diagnosis (74%) and were in first recurrence (72%). 

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Patients received up to 5 cycles of dinutuximab, an anti-GD2 antibody, in combination with GM-CSF. Thirty patients received dinutuximab on a 2-day infusion schedule — 35 mg/m2 per day over 20 hours. Nine patients received dinutuximab on a 4-day infusion schedule — 17.5 mg/m2 per day over 10 hours. 

The primary endpoint was DCR, which was defined as the proportion of patients who were event-free 12 months after enrollment. The DCR was 28.2%, which did not meet the threshold for efficacy set by the historical benchmark.2 

According to the benchmark, dinutuximab plus GM-CSF would be considered effective if at least 16 of the 39 patients were event-free at 12 months. However, only 11 patients remained event-free at 12 months. 

Dinutuximab plus GM-CSF did meet criteria for unacceptable toxicity, as there was 1 sudden death on study. Though the cause of death is unknown, it is likely related to study treatment, according to the researchers.

Other grade 3 or higher adverse events with the 2-day and 4-day infusion schedules, respectively, included abdominal pain (23% vs 56%), diarrhea (10% vs 11%), hypoxia (23% vs 44%), and hypotension (27% vs 22%). 

All patients on the 4-day infusion schedule experienced grade 3 or higher toxicities, whereas most patients on the 2-day schedule did not (76.7%). Pharmacokinetics were similar with the 2 schedules.

The researchers noted that, although dinutuximab plus GM-CSF did not improve DCR in this study, other strategies for targeting GD2 are being developed.

Disclosures: The dinutuximab used in this study was supplied by United Therapeutics. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


1. Hingorani P, Krailo M, Buxton A, et al. Phase 2 study of anti-disialoganglioside antibody, dinutuximab, in combination with GM-CSF in patients with recurrent osteosarcoma: A report from the Children’s Oncology Group. Eur J Cancer. Published online July 6, 2022. doi:10.1016/j.ejca.2022.05.035

2. Lagmay JP, Krailo MD, Dang H, et al. Outcome of patients with recurrent osteosarcoma enrolled in seven phase II trials through Children’s Cancer Group, Pediatric Oncology Group, and Children’s Oncology Group: learning from the past to move forward. J Clin Oncol. 2016;34(25):3031-3038. doi:10.1200/JCO.2015.65.5381