Long‐term analysis of children with metastatic neuroblastoma treated in the ENSG5 randomised clinical trial

Abstract

Background The European Neuroblastoma Study Group 5 (ENSG5) trial showed that time‐intensive “rapid” induction chemotherapy (COJEC) was superior to “standard” 3‐weekly chemotherapy for children with high‐risk metastatic neuroblastoma. Long‐term outcomes of the ENSG5 trial were analysed. Procedure Patients with metastatic neuroblastoma aged ≥12 months were randomly assigned to “standard” or “rapid” induction, receiving the same chemotherapy drugs and doses. Event‐free survival (EFS) and overall survival (OS) were analysed and prognostic factors evaluated. Amongst patients surviving >5 years, a population of children with persistent metastatic disease after the end of treatment was identified and described. Results Ten‐year EFS was 18.2% (95% confidence interval: 12.2–25.2) for the “standard” arm and 26.8% (19.5–34.7) for the “rapid” arm (hazard ratio [HR] 0.85, P = 0.28). Ten‐year OS for the “standard” arm was 19.7% (13.4–26.8) and 28.3% (20.8‐36.2) for the “rapid arm” (HR 0.83, P = 0.19). There was a trend for worse EFS and OS for patients having MYCN amplification (HR 1.37 and 1.40, respectively) and those with partial and mixed response to induction (HR 1.69 and 1.75 for EFS and 1.66 and 2.00 for OS, respectively). Among 69 patients who survived >5 years, six had persistent metastatic disease after the end of treatment. Conclusion The benefit of the “rapid” induction regimen seems to be maintained in the long term, although the small number of survivors could justify the lack of statistical significance. MYCN amplification and poor metastatic response to induction could be associated with worse outcomes. A small group of patients with persistent metastatic disease that survived long term has been described.

Clinically relevant treatment of PDX models reveals patterns of neuroblastoma chemoresistance

“…An established regimen to treat high-risk NB is the one set by the International Society of Pediatric Oncology–European Neuroblastoma (SIOPEN) ( 2 , 3 ). Rapid COJEC is the induction chemotherapy step established by SIOPEN ( 3 , 4 ). COJEC consists of high doses of five chemotherapeutic drugs (cisplatin, carboplatin, cyclophosphamide, etoposide, and vincristine) distributed in three courses that are alternatively administered in eight 10-day cycles.…”

Two bullets in the gun: combining immunotherapy with chemotherapy to defeat neuroblastoma by targeting adrenergic-mesenchymal plasticity

“…The International Society of Paediatric Oncology Europe Neuroblastoma Group (SIOPEN) developed the Rapid COJEC regimen as an induction chemotherapy step ( 29 , 30 ). The regimen consists of a combination of five chemotherapeutic drugs (cisplatin, carboplatin, cyclophosphamide, etoposide and vincristine) spread over three cycles, administrated alternatively in eight 10-days cycles ( 29 , 30 ). Most high-risk NB patients relapse after an initial response to treatment and develop therapy-resistant tumours.…”

MXD3 antisense oligonucleotide with superparamagnetic iron oxide nanoparticles: A new targeted approach for neuroblastoma

“…1 The outcome of patients with a high-risk phenotype is poor, with a survival rate of about 50%. 2,3 Therefore, there is an urgent need for more effective treatments for NB.…”