Efficacy and safety of palonosetron versus ondansetron for preventing chemotherapy-induced nausea and vomiting: a systematic review and meta-analysis of randomised controlled trials

Abstract Background 5-hydroxytryptamine type 3 receptor antagonists (5HT₃RAs) are widely used to prevent chemotherapy-induced nausea and vomiting (CINV). Although previous meta-analyses have demonstrated that palonosetron offers superior efficacy over first-generation 5HT₃RAs, direct comparisons with ondansetron remain limited and earlier analyses may not reflect more recent evidence. This systematic review and meta-analysis aimed to evaluate the comparative efficacy and safety of palonosetron versus ondansetron using randomised controlled trials (RCTs) providing head-to-head comparisons between the two agents. Methods A systematic search was conducted across PubMed, Cochrane Library and Scopus. The primary outcome was complete response (CR), while complete control (CC) and adverse events were the secondary outcomes. A meta-analysis was performed using the Restricted Maximum Likelihood estimator and the Hartung-Knapp-Sidik-Jonkman correction. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool, and certainty of evidence was evaluated using the GRADE approach. Results Eight RCTs with a total of 1,741 patients were included in the meta-analysis. Palonosetron was associated with higher CR rates than ondansetron during the acute (RR 1.10, 95% CI 1.04–1.15), delayed (RR 1.22, 95% CI 1.13–1.32) and overall phases (RR 1.28, 95% CI 1.20–1.36). There were no significant differences for CC rates in the acute (RR 1.09, 95% CI 0.82–1.44), delayed (RR 1.17, 95% CI 0.86–1.58) and overall phases (RR 1.08, 95% CI 0.98–1.19). For adverse events, no significant differences were found for headache (RR 0.88, 95% CI 0.68–1.14), constipation (RR 1.47, 95% CI 0.67–3.25) or dizziness (RR 0.71, 95% CI 0.32–1.59). Conclusions Palonosetron was associated with significantly higher CR rates than ondansetron across the acute, delayed, and overall phases. No significant differences were observed in the reported adverse events; however, the available safety data were limited, and the absence of statistically significant differences should not be interpreted as evidence of comparable safety between the two agents. Registration CRD420251108042.