NIAGARA
In cisplatin-eligible operable MIBC, does perioperative durvalumab + gemcitabine/cisplatin improve EFS and OS?
Biomarker / PD-L1
PD-L1 was a prespecified stratification factor and was assessed with the VENTANA PD-L1 SP263 assay using the TC/IC25% algorithm. PD-L1-high was defined as ≥25% of tumour cells with membrane staining, or qualifying immune-cell staining (≥25% when immune cells involved >1% of tumour area, or 100% when immune cells involved 1%). Approximately 73% were PD-L1-high and 27% low/negative. EFS benefit was reported across prespecified PD-L1 strata; the trial was not restricted to PD-L1-high disease.
Absolute Effect
EFS: HR 0.68 (95% CI 0.56–0.82), P<.001. EFS included progression, recurrence, failure to undergo cystectomy, or death.
pCR: The trial did not show a statistically significant difference in pathological complete response, despite significant EFS and OS improvement.
Surgery: Radical cystectomy was performed in 88.0% vs 83.2%.
Safety: Grade 3–4 treatment-related AEs were 40.6% vs 40.9%; treatment-related death 0.6% in each arm.
Interpretation & limitations
The benefit is a perioperative strategy effect, not simply a neoadjuvant immunotherapy effect, because durvalumab continued after cystectomy. The trial was open-label and limited to cisplatin-eligible patients.
Primary source
Powles T, et al. N Engl J Med. 2024;391:1773–1786.