Efficacy/Safety of Palonosetron Vs Ondansetron in Preventing Chemotherapy-Induced Nausea and Vomiting (Cinv) in Pediatric Patients Receiving Moderately or Highly Emetogenic Chemotherapy (Mec/Hec)

Abstract

ABSTRACT Aim: Evaluate the efficacy and safety of two dose-levels of palonosetron (PALO) vs ondansetron (the standard of care comparator) in the prevention of CINV in pediatric patients receiving MEC/HEC in a multicenter, multinational, randomized, double-blind study. Methods: Patients with malignant disease scheduled to receive MEC/HEC were randomized to receive PALO (low-dose: 10 mcg/kg, maximum dose 0.75 mg; high-dose: 20 mcg/kg, maximum dose 1.5 mg) or ondansetron (3 x 150 mcg/kg, maximum dose 32 mg). The primary objective was to demonstrate the non-inferiority of PALO (d=-15%) vs ondansetron in terms of patients with a complete response (CR: no emesis/rescue medication) in the acute phase (0–24h after chemotherapy administration). Secondary objectives included CR rate in the delayed (25–120h) and overall (0–120h) phases, safety and tolerability. Results: A total of 502 patients were randomized and 493 included in the full analysis set (166 low-, 165 high-dose PALO; 162 ondansetron). Aged between 64 days and 16.9 years, the majority of patients were male (53.1%) and white (95.1%). The CR rate (acute phase) was 54.2% and 59.4% for low- and high-dose PALO patients, and 58.6% for ondansetron patients. Statistical analysis confirmed non-inferiority for high-dose PALO. The CR rate (delayed phase) was 28.9% and 38.8% in the low- and high-dose PALO groups, and 28.4% in the ondansetron group, with similar results in the overall phase. Treatment-emergent adverse events (TEAEs) were 80.2% and 69.3% in the low- and high-dose PALO groups, and 81.7% in the ondansetron group. The most frequently reported drug-related TEAE was headache (low-dose PALO: 1.8%; high-dose PALO: 0.6%; ondansetron: 1.2%). Three patients (1 high-dose PALO; 2 ondansetron) also experienced prolonged QTc intervals, but these events were considered to be non-serious. All withdrawals and/or deaths were unrelated to the study drug. Conclusions: High-dose PALO is efficacious for the prevention of CINV in pediatric patients receiving HEC, and non-inferior to ondansetron as supported by statistical analyses. The safety profiles raised no concerns. Disclosure: T. Spinelli: Tulla Spinelli is an employee of Helsinn Healthcare SA; P. Nicolas: Pierre Nicolas is an employee of Helsinn Healthcare SA. All other authors have declared no conflicts of interest.