Abstract:Objective To investigate the efficacy of different neurokinin- 1（NK-1）receptor antagonists（aprepitant，fosaprepitant，netupitant）in preventing acute and delayed nausea and vomiting in patients receiving highly emetogenic chemotherapy（HEC），and to compare the safety differences among the three agents. Methods This study was a randomized controlled clinical trial，involving 129 patients who received HEC at the Provincial Hospital Affiliated to Shandong First Medical University from November 2023 to May 2024. The patients were randomly divided into an aprepitant group（n=43），a fosaprepitant group（n=43），and a netupitant group（n=43）. The incidence of acute and delayed nausea and vomiting within 0 to 120 hours after chemotherapy and the Visual Analogue Scale（VAS）scores at the time of acute and delayed nausea and vomiting were recorded for each group. The efficacy，discontinuation rate，and occurrence of adverse events were compared among the three groups. Multivariate logistic regression was used to analyze the factors influencing complete response （CR） in patients receiving HEC. Results There was no statistically significant difference in the incidence of acute nausea，acute vomiting，delayed nausea，and delayed vomiting among the three groups（P＞0.05）. The CR rate was 74.42% in the aprepitant group，67.44% in the fosaprepitant group，and the highest at 76.74% in the netupitant group，with no statistically significant difference among the three groups（χ2=1.019，P=0.601）. There was no statistically significant difference in the incidence of headache，constipation，fatigue，and serious adverse events among the three groups（P＞0.05）. The discontinuation rates of the aprepitant，fosaprepitant and netupitant groups were 9.30%，13.95% and 6.98%，respectively，with no statistical difference（χ2=1.198，P=0.550）. Multivariate logistic regression analysis showed that age，gender，chemotherapy dosage，drug type，and tumor type were not influencing factors for CR（P＞0.05）. Conclusion Aprepitant，fosaprepitant，and netupitant have comparable efficacy in preventing acute and delayed nausea and vomiting induced by HEC，and all three agents demonstrate a favorable safety profile.