Randomized, double-blind phase III trial of a dexamethasone-free regimen for managing highly emetogenic chemotherapy-induced nausea and vomiting.

Chemotherapy-induced nausea and vomiting (CINV) remains a prevalent treatment complication, often significantly impairing patients' quality of life and reducing adherence to chemotherapy regimens. The standard triplet antiemetic regimen, including either a neurokinin-1 (NK1) receptor antagonist (RA) or olanzapine, combined with a 5-hydroxytryptamine type 3 (5-HT3) RA and dexamethasone (DEX), faces challenges primarily due to DEX-related adverse effects and its potential to compromise the efficacy of antitumor agents. This study assessed whether omitting DEX (F-Group: olanzapine + 5-HT3 RA) is non-inferior to the standard D-Group (olanzapine + 5-HT3 RA + DEX). In this multi-center, double-blind, randomized phase III trial, 254 adults with malignant solid tumors (Eastern Cooperative Oncology Group [ECOG] 0-2) scheduled for highly emetogenic chemotherapy (HEC) were randomized 1:1 to the F-Group or D-Group. The primary endpoint was the complete response (CR; no emesis/rescue medication) rate over 0-120 h, with a non-inferiority margin of -15%. Secondary endpoints included CR and complete control (CC; no vomiting/nausea/rescue therapy) rates in acute (0-24 h) and delayed (25-120 h) phases, safety, and quality of life. Overall CR rates were 68.6% (D-Group) and 69.7% (F-Group; p = .9658), demonstrating non-inferiority. Acute phase CR rates were 88.4% versus 86.9% (p = .8643), and delayed phase CR rates were 69.4% versus 69.7% (p > .9999). CC rates were comparable across phases, with no new adverse reactions. The combination of a 5-HT3 RA and olanzapine is as non-inferior as the standard triplet regimen, providing an alternative option for patients receiving HEC. The trial was registered at ClinicalTrials.gov, number NCT05805800.