A systematic review and meta-analysis on evaluating the efficacy and safety of netupitant/palonosetron compared to aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients undergoing emetogenic chemotherapy.
Authors: Bibi Maryam, Muhammad Shahzil, Debduti Mukhopadhyay, Mariyah Zainab Irfan, Anza Muhammad, Faiza Khan, Aqsa Ashraf
Journal: Journal of Clinical Oncology (2025)

823 Background: NEPA stands as the exclusive oral fixed combination antiemetic agent, comprising the highly selective NK1 receptor antagonist (RA) netupitant (300 mg) and the clinically distinct 5-HT3 RA, palonosetron (0.5 mg). Administered in a single dose, NEPA concurrently modulates two critical antiemetic pathways, offering a more convenient and straightforward alternative for sustained protection against chemotherapy-induced nausea andvomiting (CINV). Numerous studies have assessed NEPA's efficacy relative to other Neurokinin (NK) 1 receptor antagonists (RAs), notably aprepitant (APR), widely utilized for CINV. Our study critically examines the efficacy and safety of NEPA versus APR for preventing CINV in patients receiving emetogenic chemotherapy, drawing insights from recent studies. Methods: Studies comparing NEPA versus APR for the prevention of CINV in patients receiving emetogenic chemotherapy until August 2024 were systematically searched on Medline, Embase, and Cochrane Library. Notably, no systematic review or meta-analysis of pooled data from existing studies is currently present in the literature. Results: Following screening, four studies were deemed eligible for inclusion in the meta-analysis, encompassing a total of 2079 patients. The NEPA group comprised 1047 individuals, while the APR group comprised 1032 subjects. The primary outcome included the comparison of subjects experiencing no nausea in overall phases. Secondary outcomes involved subjects with no emesis and no nausea in the acute and delayed phases. A significant reduction in the risk of overall nausea in the NEPA group was observed compared to the APR group after Moderately Emetogenic Therapy (MEC) or Highly Emetogenic Therapy (HEC) [Risk Ratio (RR) of 1.07, 95% Confidence Interval (CI) = 1.01-1.13, P = 0.01). A trend of reduced emesis during both acute [RR = 1.08, 95% CI = 0.95-1.22, P = 0.24] and delayed periods [RR = 1.03, 95% CI = 0.99-1.07, P = 0.15] was observed in the NEPA group, but the results were not statistically significant. Significant nausea in the acute and delayed post-chemotherapy periods exhibited a similar trend (RR = 1.02, 95% CI = 0.98-1.06, P = 0.43) and (RR = 1.04, 95% CI = 0.98-1.10, P = 0.23) respectively, with non-significant statistical outcomes. Conclusions: Our analysis suggests that the use of NEPA results in better control of nausea in overall phases compared to Aprepitant for the prevention of CINV in patients receiving emetogenic chemotherapy. However, NEPA demonstrates comparable efficacy to aprepitant in achieving control of nausea and emesis when the symptoms are stratified in acute and delayed phases. Nevertheless, further studies are warranted for a comprehensive comparison between NEPA and Aprepitant for the prevention of CINV.