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For patients receiving highly emetogenic chemotherapy (HEC), current guidelines recommend a four-drug antiemetic regimen that includes dexamethasone. But this drug has well-known side effects, and even a short course can blunt antitumor immune responses. Now that more-potent antiemetics are available, do patients still need 4 days of dexamethasone?
In this phase 3, multicenter, open-label, noninferiority trial, 644 adults receiving HEC in China were randomized to receive standard dexamethasone (12 mg on day 1; 8 mg on days 2–4), limited dexamethasone (6 mg on day 1 only), or no dexamethasone. All three groups received netupitant–palonosetron on day 1 and olanzapine 5 mg daily on days 1–4.
The percentage of patients achieving complete response (no emesis and no rescue medication over 120 hours) was similar across groups: 72% with standard dexamethasone, 72% with limited dexamethasone, and 70% with no dexamethasone.
Omitting dexamethasone led to modestly worse nausea control on days 1–3 (with half the patients reporting an impact on their daily life, compared with one third of the other groups), but the difference resolved by day 4.
Steroid-related side effects were less frequent and less severe in the two reduced-steroid arms.
Meng Y, et al. Reduced/no dexamethasone with netupitant/palonosetron and olanzapine for chemotherapy-induced nausea/vomiting in highly emetogenic chemotherapy: Phase III noninferiority trial. J Clin Oncol 2026 Jun 4; [e-pub]. DOI: 10.1200/JCO-26-01029. PubMed
Industry funded: No
Comment
This trial makes a compelling case that for most patients on HEC, a single 6-mg dose of dexamethasone strikes the right balance between nausea control and steroid-associated adverse events. Complete dexamethasone omission was noninferior but didn’t suppress early nausea; this is concerning not only because of immediate tolerability but also because poor control during one cycle increases the risk for nausea in later cycles. Reducing dexamethasone, but not omitting it, seems to be the key here.