Phase III Trial: Single Low-Dose 5 mg Dexamethasone with NEPA for Preventing 168 h Nausea and Vomiting of Diverse Highly or Moderately Emetogenic Chemotherapy (LD-NEPA)

Background/Objectives: Reducing corticosteroid exposure has become an important objective in the management of chemotherapy-induced nausea and vomiting (CINV), given the dose-related toxicity of dexamethasone (DEX). This prospective phase III randomized (LD-NEPA: low-dose dexamethasone plus netupitant/palonosetron) study evaluated whether a reduced dose of 5 mg DEX could maintain antiemetic efficacy when combined with NEPA in patients receiving highly or moderately emetogenic chemotherapy (HEC/MEC). Methods: Adult patients were randomly assigned (1:1) to receive NEPA with either 5 mg DEX (5D group) or 8 mg DEX (8D group). Among 186 randomized patients, 180 were included in the analysis (89 in the 5D group and 91 in the 8D group). The primary endpoint was the complete response rate (CRR; no emesis and no rescue medication use) during the 0–168 h period. Secondary endpoints included phase-specific CRR, total control rate (TCR), complete control rate (CCR), daily incidence of nausea and vomiting, and safety outcomes. Results: The overall CRR was 78.7% in the 5D group and 70.3% in the 8D group. The between-group difference was 8.4% (95% CI: −1.5% to 19.0%), demonstrating the reduced-dose regimen was non-inferior, with the lower bound exceeding the prespecified −15% margin. Consistent results were observed across secondary endpoints. Treatment-related adverse events were mostly grade 1–2 and occurred with broadly comparable frequencies between the two groups. Conclusions: A single lower dose of 5 mg DEX is noninferior to an 8 mg dose combined with NEPA for preventing 168 h nausea and vomiting of diverse HEC/MEC, offering comparable efficacy while reducing corticosteroid exposure.