Reducing or omitting dexamethasone with NEPA and olanzapine for prevention of chemotherapy-induced nausea and vomiting in highly emetogenic chemotherapy: a randomized non-inferiority phase III trial.

Meng, Yanchun; Liu, Yingying; Lin, Mingxi; Wang, Lili; Mu, Yuxin; Yang, Ling; Du, Yiqun; Liu, Xiaojun et al. · J Clin Oncol · 2026

rct · Level II

Where this comes from

Abstract

Guideline-recommended 4-day dexamethasone (DEX) for highly emetogenic chemotherapy (HEC) raises toxicity and immunotherapy interference concerns. We tested whether DEX reduction or omission with NEPA (netupitant/palonosetron) plus olanzapine is non-inferior to standard DEX. In this open-label, randomized phase III non-inferiority trial across 28 Chinese centers, adults receiving HEC received NEPA (day 1) plus olanzapine (days 1-4) and were randomized to standard DEX (12 mg day 1, 8 mg days 2-4), DEX-sparing (6 mg day 1 only), or DEX-free (no DEX). Primary endpoint was complete response (CR; no emesis/no rescue medication) from 0-120 hours. Non-inferiority margin was -12% (one-sided α=.025). Of 644 randomized patients (median age 54.9 years; 66.0% female), stratified analysis showed overall CR rates of 72.4% for standard, 72.2% for DEX-sparing (stratified risk difference [RD] -0.2%; 95% CI, -8.7% to 8.5%; P<sub>non-inferiority</sub>=.005), and 70.1% for DEX-free (stratified RD -2.2%; 95% CI, -10.7% to 6.4%; P<sub>non-inferiority</sub>=.014). Both met non-inferiority, confirmed in per-protocol analysis. Steroid-related toxicities were significantly lower with DEX-sparing and DEX-free regimens versus standard. NEPA plus olanzapine with reduced (6 mg day 1 only) or no DEX is non-inferior to standard 4-day DEX for CINV prevention in HEC, supporting steroid-sparing strategies particularly relevant in the chemo-immunotherapy era.