Aprepitant versus a single dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: A randomized, parallel-group, phase III trial

Abstract

Abstract BACKGROUND: For the recent prevention of chemotherapy-induced nausea and vomiting (CINV) in children aged 6 months and older, neurokinin-1(NK-1) receptor antagonists were suggested. However, there is little information available on how to select NK-1 receptor antagonists for pediatric patients, such as aprepitant and fosaprepitant. METHODS: Children between the ages of 2 and 12 who were scheduled to undergo chemotherapy that was either mildly or strongly emetic were randomly randomized to receive fosaprepitant (arm-A) or aprepitant (arm-B). For the children in arm-A, ondansetron and dexamethasone were administered intravenously, followed by a fosaprepitant infusion. The identical medications were administered to children selected for arm-B, with the exception that aprepitant was used instead of fosaprepitant. Dexamethasone and ondansetron were continuously administered for 48 hours following the conclusion of treatment. The proportion of patients who experienced a complete response (CR), which is defined as no vomiting, no retching, and no need for rescue medication, during the acute phase (0-24 hours after the last dose of chemotherapy) was administered, was the study's main end point. The percentage of patients who achieved a CR overall and within the delayed period (24-120 hours) following the last chemotherapy treatment were considered secondary end goals. RESULTS : A total of 108 patients were examined (55 in the fosaprepitant arm and 53 in the aprepitant arm). In the acute phase (95% vs 79%, P =0.018, P<0.05), delayed phase (71% vs 66%, P =0.586), and overall phase (69% vs 57%, P =0.179), CR rates were greater in the fosaprepitant arm than in the aprepitant arm. Additionally, there is no difference between the aprepitant arm (11%) and the fosaprepitant arm (7%) in terms of the desire for rescue anti-emetics. CONCLUSIONS: Adding fosaprepitant to ondansetron and dexamethasone is more beneficial than adding aprepitant for preventing CINV in the acute phase. Fosaprepitant and aprepitant, however, do not significantly differ from one another for prevention throughout the delayed and overall phases. This study was approved by IRB of Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine (No. SCMCIRB-K2020120-2), and it was prospectively registered with the ClinicalTrials.gov on April 22, 2021 (reference number: NCT04873284 ).