Dexamethasone-Free Antiemetic Prophylaxis for Highly Emetogenic Chemotherapy: A Double-Blind, Phase III Randomized Controlled Trial (CINV POD study)

Abstract

PURPOSEThe effectiveness of a dexamethasone (DEX)-free regimen for chemotherapy-induced nausea and vomiting (CINV) prophylaxis in patients receiving highly emetogenic chemotherapy (HEC) is not known.METHODSThis was a double-blind, phase III trial designed to show the noninferiority of a DEX-free regimen (olanzapine, palonosetron, and fosaprepitant [OPF]) compared with the DEX-containing regimen (olanzapine, palonosetron, and DEX [OPD]). Chemotherapy-naïve patients age 18-80 years receiving single-day HEC were randomly assigned 1:1 to receive either the OPD regimen or the OPF regimen. The primary objective was to compare complete response (CR) rates for vomiting during the overall period (start of chemotherapy to 120 hours). Secondary objectives included CR for vomiting during the acute period (0-24 hours) and delayed period (24-120 hours), CR for nausea, and comparison of toxicities and patient-reported outcomes.RESULTSThree hundred forty-six patients received the study interventions, 174 in the OPD arm and 172 in the OPF arm. The DEX-free OPF arm had significantly higher CR rates for vomiting compared with the DEX-containing OPD arm in acute (94.7% v 85.6%; P < .004), delayed (81.9% v 50.5%; P < .001), and overall (79.6% v 48.8%; P < .001) periods. For nausea, CR rates in the OPF arm were higher in delayed (53.4% v 39.6%; P = .009) and overall (50.5% v 39.1%; P = .031) periods but not in the acute period (77.9% v 81.6%; P = .39). Fatigue (P = .009) and drowsiness (P = .002) were more in the OPF arm in the acute period and insomnia (P < .001) in the OPD arm in the overall period.CONCLUSIONThis study shows that a DEX-free OPF regimen is efficacious and should be considered a standard option for acute and delayed CINV prophylaxis for HEC.