A multicycle phase III study evaluating palonosetron vs ondansetron at preventing chemotherapy-induced nausea and vomiting in pediatric patients

Background: Palonosetron is non-inferior to ondansetron at preventing chemotherapy-induced nausea and vomiting (CINV) in adult patients receiving moderately/highly emetogenic chemotherapy (MEC/HEC). This multinational double-blind study evaluated efficacy and safety of two palonosetron doses vs ondansetron in pediatric patients receiving up to four cycles of MEC/HEC.

Materials and Methods: Patients scheduled to receive MEC/HEC were randomized to receive intravenous palonosetron (10, 20µg/kg) or ondansetron (3×150µg/kg). For the primary objective statistics were used to show non-inferiority for palonosetron (δ=-15%) vs ondansetron from complete response rates (CR: no vomiting/retching/rescue medication) during the acute phase (0–24h after the first MEC/HEC dose) of cycle 1. Secondary objectives included CR rate during the delayed (>24–120h) and overall (0–120h) phases, the proportion of patients without vomiting and safety.

Results: Of 502 patients randomized, 493 aged 2.1 months to 16.9 years were included in the full analysis set. CR rates were highest in the palonosetron 20µg/kg group during all phases of cycles 1, 3 and 4 with non-inferiority shown for this dose vs ondansetron during the acute phase of cycle 1 (97.5% CI −11.7–12.4; p=0.0022). In cycle 1 reports of no vomiting (see table) were higher in the palonosetron groups vs the ondansetron group during all phases with proportions in the palonosetron 20µg/kg group >10% higher. In cycles 2–4 reports of no vomiting were consistently higher in the palonosetron 20µg/kg group vs the ondansetron group during all phases.

In cycles 1–4 treatment-emergent adverse events (TEAEs, %) were fewer in the palono­setron 20µg/kg group (69.3, 64.4, 55.9, 48.4) vs the palonosetron 10µg/kg (80.2, 76.2, 72.1, 75.0) and ondansetron (81.7, 82.6, 68.2, 72.2) groups. All withdrawals/fatal TEAEs were not deemed drug-related. Electrocardiogram evaluations raised no concerns.

Conclusions: In pediatric patients receiving up to four cycles of MEC/HEC, intravenous palonosetron 20µg/kg has shown non-inferiority vs ondansetron during the acute phase of cycle 1, numerical superiority vs ondansetron during all phases of cycles 1–4 for no vomiting rates, and presented no significant safety risks.

Conflict of interest: Other Substantive Relationships: Edita Kabickova and Antonio Wachtel have had travel, accommodation and/or other expenses paid for by Helsinn Healthcare SA. Tulla Spinelli and Pierre Nicolas are employees of Helsinn Healthcare SA. Gabor Kovacs has received honoraria from Helsinn Healthcare SA.