Neurokinin-1 Receptor Antagonist-Based Triple Regimens in Preventing Chemotherapy-Induced Nausea and Vomiting: A Network Meta-Analysis

Background: Neurokinin-1 receptor antagonists (NK-1RAs) are widely used for chemotherapy-induced nausea and vomiting (CINV) control in patients with highly emetogenic chemotherapy (HEC) and/or moderately emetogenic chemotherapy (MEC). Whether the efficacy and toxicity of antiemesis are different among various NK-1RA-based triple regimens is unknown. Methods: Data of complete responses (CRs) in the acute, delayed, and overall phases and treatment-related adverse events (TRAEs) were extracted from electronic databases. Efficacy and toxicity were integrated by pairwise and networkmeta-analyses. Results: Thirty-six trials involving 18 889 patients using triple regimens (NK-1RA+serotonin receptor antagonists [5HT3RA] + dexamethasone) or duplex regimen (5HT3RA+dexamethasone) to control CINV were included in the analysis. Different NK-1RA-based triple regimens shared equivalent effect on CRs. In patients with HEC, almost all triple regimens showed statistically significantly higher CRs than duplex regimen (odds ratio [OR](duplex/triple) = 0.47-0.66). However, in patients with MEC, only aprepitant-based triple regimen showed better effect than duplex regimen statistically significantly in CRs (ORduplex/triple = 0.52, 95% confidence interval [CI] = 0.34 to 0.68). No statistically significant difference of TRAEs was found among different triple regimens. Palonosetron-based triple regimens were equivalent to first-generation 5HT3RAs-based triple regimens for CRs. Moreover, different doses of dexamethasone plus NK-1RA and 5HT3RA showed no statistically significant difference in CRs. Conclusions: Different NK-1RAs-based triple regimens shared equivalent effect on CINV control. Various triple regimens had superior antiemetic effect than duplex regimen in patients with HEC. Only aprepitant-based triple regimen showed better CINV control compared with duplex regimen in patients receiving MEC. Palonosetron and first-generation 5HT3RAs might share equivalent CINV control in the combination of NK-1RAs and dexamethasone. Lower doses of dexamethasone might be applied when used with NK-1RAs and 5HT3RAs.