Palonosetron vs ondansetron: Prevention of chemotherapy-induced nausea and vomiting in pediatric patients in a multicycle study.

Background: Palonosetron (PALO) has been shown to be non-inferior to ondansetron (OND) at preventing chemotherapy-induced nausea and vomiting (CINV) in adult patients (pts) receiving moderately/highly emetogenic chemotherapy (MEC/HEC). Methods: This phase III study evaluated the efficacy/safety of two PALO doses (10, 20 µg/kg) vs OND (3 × 150 µg/kg) in pediatric pts receiving up to 4 MEC/HEC cycles. For the primary objective statistical analysis was used to show non-inferiority for PALO (δ = -15%) vs OND from complete response rates (CR, no emesis/rescue medication) in the acute phase (0–24h after first MEC/HEC dose) of cycle 1. Secondary objectives included CR rate in the delayed (>24–120h) and overall (0–120h) phases and safety. Results: In 493 pts aged 64 days–16.9 years the CR rate was highest in the PALO 20 µg/kg group in all phases of cycles 1, 3 and 4 with statistical non-inferiority shown for this dose vs OND in the acute phase of cycle 1 (see table). In cycles 1–4 treatment-emergent adverse events (TEAEs) were fewer in the PALO 20 µg/kg group (69.3%, 64.4%, 55.9%, 48.4%) vs the PALO 10 µg/kg (80.2%, 76.2%, 72.1%, 75.0%) and OND (81.7%, 82.6%, 68.2%, 72.2%) groups. Drug-related TEAEs (cycles 1–2 only) were comparable although highest in the OND group (4.7%). TEAEs in cycles 3–4 plus all study withdrawals and fatal TEAEs were not considered drug-related. Laboratory and ECG evaluations, inclusive of the QT interval raised no concerns. Conclusions: In pediatric pts receiving up to 4 MEC/HEC cycles palonosetron 20 µg/kg was non-inferior to OND in the acute phase of cycle 1, numerically superior to OND across all cycles and presented no significant safety risks.

Clinical trial information: NCT01442376