Dexamethasone-Free Antiemetic Prophylaxis for Children and Adolescents Receiving Highly Emetogenic Chemotherapy: A Multicenter, Phase III, Noninferiority Trial (CIVIC POD)
In brief
Olanzapine without dexamethasone matches standard vomiting control (63% vs 57%) in children
In a phase III trial of 310 kids receiving highly emetogenic chemotherapy, an olanzapine-palonosetron-fosaprepitant regimen achieved a complete response to vomiting in 63.5% of patients, non-inferior to the dexamethasone-based standard (56.9%). Nausea control was similar, but somnolence was more common with olanzapine, highlighting a trade-off for steroid-sparing therapy.
- Journal
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology (Q1)
- Published
- 30 July 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Venkatraman Radhakrishnan, Prasanth Srinivasan, Gargi Das, Sameer Bakhshi, Amita Mahajan, Prasanth Ganesan, et al.
- PMID
- 42535876
- DOI
- 10.1200/JCO-26-00677
Why clinicians should know about it
- Picked for Pediatrics and Child Health (top studies of the week, 2 August 2026): High-quality evidence in a top journal
- Picked for Oncology and Radiation Oncology (paper of the day, 1 August 2026): Phase III non‑inferiority trial of dexamethasone‑free antiemetic regimen
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.