Dexamethasone-Free Antiemetic Prophylaxis for Children and Adolescents Receiving Highly Emetogenic Chemotherapy: A Multicenter, Phase III, Noninferiority Trial (CIVIC POD)

Abstract

PURPOSE Dexamethasone combined with a 5-hydroxytryptamine-3 receptor antagonist and a neurokinin-1 receptor antagonist is the guideline-recommended prophylaxis for chemotherapy-induced nausea and vomiting (CINV) in children receiving highly emetogenic chemotherapy (HEC), but it is associated with clinically relevant toxicities. The role of olanzapine as a dexamethasone-sparing agent for pediatric CINV prophylaxis remains uncertain. METHODS The Chemotherapy Induced Vomiting in Children-Prophylaxis Omitting Dexamethasone (CIVIC POD) was an investigator-initiated, multicenter, open-label, phase III, randomized noninferiority (NI) trial (INPHOG-SUPP-22-03) that enrolled patients age 4-18 years scheduled to receive single- or multiday HEC. Patients were randomly assigned 1:1 to dexamethasone, palonosetron, and fosaprepitant (DEX) or olanzapine, palonosetron, and fosaprepitant (OLANZ) for one chemotherapy cycle. The primary end point was complete response (CR) to vomiting (no vomiting and no rescue antiemetics) during the overall period (0-120 h after last chemotherapy). The prespecified NI margin was –15%. RESULTS A total of 310 patients were randomly assigned (DEX, n = 156; OLANZ, n = 154). The median age was 13 years, 62.3% were male, and 51.9% received multiday chemotherapy. The per-protocol population included 299 patients (DEX, n = 151; OLANZ, n = 148). The overall-period CR to vomiting was 56.9% with DEX and 63.5% with OLANZ (absolute difference, 6.6% [95% CI, −4.5 to 17.7]), meeting NI criteria. Acute-period CR to vomiting was 64.2% versus 68.9%, and delayed-period CR was 78.8% versus 79.1% (DEX v OLANZ). CR to nausea during the overall, acute, and delayed periods was 54.3% versus 53.4%, 59.6% versus 59.5%, and 69.5% versus 68.9%, respectively. Any-grade somnolence was more frequent with OLANZ (50.7% v 17.2%). CONCLUSION A dexamethasone-free regimen using olanzapine demonstrated noninferior control of vomiting compared with standard prophylaxis in children and adolescents receiving HEC, supporting olanzapine as a potential corticosteroid-sparing alternative for pediatric CINV prophylaxis.