Background
Open-label, randomized phase 3 non-inferiority trial across 28 Chinese centers (N=644). Adults receiving highly emetogenic chemotherapy (HEC), testing whether reducing or omitting dexamethasone (DEX) when NEPA (netupitant/palonosetron) plus olanzapine is used maintains antiemetic control while lowering steroid toxicity and immunotherapy interference.
Results
Interventions and follow up: All patients received NEPA (day 1) plus olanzapine (days 1–4), randomized 1:1:1 to:
Arm A (standard DEX): DEX 12 mg day 1, 8 mg days 2–4.
Arm B (DEX-sparing): DEX 6 mg day 1 only.
Arm C (DEX-free): no DEX.
Primary endpoint: complete response (CR; no emesis and no rescue medication) over 0–120 h; non-inferiority margin −12%.
mFollow up: single-cycle assessment.
Results: CR (0–120 h): standard 72.4%, DEX-sparing 72.2% (stratified risk difference −0.2%; 95% CI −8.7% to 8.5%; P(non-inferiority)=.005), DEX-free 70.1% (RD −2.2%; 95% CI −10.7% to 6.4%; P(non-inferiority)=.014). Both arms met non-inferiority, confirmed in per-protocol analysis.
Arm A (standard DEX): DEX 12 mg day 1, 8 mg days 2–4.
Arm B (DEX-sparing): DEX 6 mg day 1 only.
Arm C (DEX-free): no DEX.
Primary endpoint: complete response (CR; no emesis and no rescue medication) over 0–120 h; non-inferiority margin −12%.
mFollow up: single-cycle assessment.
Results: CR (0–120 h): standard 72.4%, DEX-sparing 72.2% (stratified risk difference −0.2%; 95% CI −8.7% to 8.5%; P(non-inferiority)=.005), DEX-free 70.1% (RD −2.2%; 95% CI −10.7% to 6.4%; P(non-inferiority)=.014). Both arms met non-inferiority, confirmed in per-protocol analysis.
Adverse events
Steroid-related toxicities: significantly lower with DEX-sparing and DEX-free regimens versus standard DEX
Grade-specific rates: NR in primary report.
Grade-specific rates: NR in primary report.
Conclusions
NEPA plus olanzapine with a single 6 mg day-1 dose of dexamethasone, or no dexamethasone, was non-inferior to standard 4-day dexamethasone for CINV prevention in HEC while reducing steroid-related toxicity, supporting steroid-sparing antiemesis — particularly relevant in the chemo-immunotherapy era.
Key Limitations
Open-label design; single Chinese-population cohort may limit generalizability; relatively wide −12% non-inferiority margin; single-cycle primary endpoint without multi-cycle durability data; olanzapine adds sedation; immunotherapy-interference benefit is inferred rather than directly measured.
Clinical Context
MASCC/ESMO and ASCO/NCCN antiemetic guidelines recommend a four-drug regimen (NK1 + 5-HT3 + dexamethasone + olanzapine) with multi-day dexamethasone for HEC. This trial provides level-1 evidence that dexamethasone can be minimized or omitted when olanzapine is included, relevant where steroids may blunt immunotherapy efficacy or worsen comorbidities.