Ramosetron Versus Ondansetron in Combination With Aprepitant and Dexamethasone for the Prevention of Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: A Multicenter, Randomized Phase III Trial, KCSG PC10-21

Abstract

Background. A combination of serotonin receptor (5- hydroxytryptamine receptor type 3) antagonists, NK-1 receptor antagonist, and steroid improves the complete response (CR) of chemotherapy-induced nausea and vomiting (CINV) in cancer patients. Ramosetron’s efficacy in this triple combination regimen has not been investigated.This prospective,multicenter, single-blind, randomized,phaseIII studycomparesacombination of ramosetron, aprepitant, and dexamethasone (RAD) with a combination of ondansetron, aprepitant, and dexamethasone (OAD) to prove the noninferiority of RAD in controlling highly emetogenic CINV. Methods. Aprepitant and dexamethasone were orally administered for both arms. Ramosetron and ondansetron were intravenouslygiventotheRADandOADgroups. Theprimaryendpoint was no vomiting and retching and no need for rescue medication duringtheacuteperiod(day1);thenoninferioritymarginwas215%. Results. A total of 299 modified intention-to-treat cancer patients who received RAD (144 patients) and OAD (155 patients) were eligible for the efficacy analysis. The CR rates ofRADversusOADwere97.2% versus 93.6% during the acute period, 77.8% versus 73.6% during the delayed period (day 2–5), and 77.1% versus 71.6% during the overall period. Furthermore, RAD was noninferior to OAD in subgroups stratified by age, cancer type, chemotherapeutic agents, and schedule. Repeated measures analysis showed that in male patients, RAD was superior to OAD. Profiles of adverse events were similar in both groups. Conclusion.RAD is as effective and tolerable as OAD for CINV prevention in patients receiving highly emetogenic chemotherapy. Ramosetron could be considered one of the best partners for aprepitant.