Kumar, Santhosh E.

ABSTRACT Background Fosaprepitant is non‐inferior to aprepitant in adults receiving highly emetogenic chemotherapy (HEC). We evaluated whether fosaprepitant is non‐inferior to aprepitant in children receiving HEC. Methods In this open‐label, non‐inferiority trial, children aged 5–18 years, receiving their first cycle of HEC, were randomized 1:1 to the fosaprepitant or aprepitant group. The fosaprepitant group received a single intravenous dose of 4 mg/kg (max 150 mg). The aprepitant group received oral aprepitant capsules (weight 15 to <30 kg: 80 mg Days 1–3; weight ≥30 kg, or age ≥12 years: 125 mg Day 1, 80 mg Days 2 and 3). Both groups received ondansetron and dexamethasone. The primary outcome was the complete response (CR) rate of vomiting during the acute phase (AP) with a non‐inferiority margin of 15%. Secondary outcomes included CR rates in the delayed (DP) and overall phases (OP), grade of vomiting, incidence and severity of nausea, and adverse effects. Results A total of 279 children were included in the modified intention‐to‐treat analysis (fosaprepitant group: 140; aprepitant group: 139). In AP, the difference of CR rate between fosaprepitant [76 (54.3%)] and aprepitant groups [84 (60.4%)] was −6.1% [90% CI: −15.7% to +3.6%], with the lower limit exceeding −15%, failing to establish non‐inferiority. The CR rate with fosaprepitant versus aprepitant was 62.1% ( n = 87) versus 65.5% ( n = 91) in DP (difference: –3.4%; 90% CI: –12.7% to 6.1%) and 42.9% ( n = 60) versus 49.6% ( n = 69) in the OP (difference: –6.7%; 90% CI: –16.5% to 3.1%). Grade of vomiting, incidence and severity of nausea, and adverse effects were similar between the two groups. Conclusions Non‐inferiority of fosaprepitant compared to aprepitant was not demonstrated in children undergoing their first cycle of HEC. Trial Registration Clinical Trials Registry, India (CTRI/2019/05/019082).