Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu klinické zkoušky, fáze III, srovnávací studie, časopisecké články, multicentrická studie, randomizované kontrolované studie, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
P30 CA008748
NCI NIH HHS - United States
P50 CA221745
NCI NIH HHS - United States
PubMed
34077643
PubMed Central
PMC8215888
DOI
10.1056/nejmoa2034442
Knihovny.cz E-zdroje
- MeSH
- adjuvantní chemoterapie MeSH
- analýza podle původního léčebného záměru MeSH
- antigeny CD274 metabolismus MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- invazivní růst nádoru MeSH
- karcinom z přechodných buněk farmakoterapie patologie chirurgie MeSH
- kvalita života MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory močového měchýře farmakoterapie patologie chirurgie MeSH
- nivolumab škodlivé účinky terapeutické užití MeSH
- placeba terapeutické užití MeSH
- přežití po terapii bez příznaků nemoci MeSH
- protinádorové látky imunologicky aktivní škodlivé účinky terapeutické užití MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Research Support, N.I.H., Extramural MeSH
- srovnávací studie MeSH
- Názvy látek
- antigeny CD274 MeSH
- nivolumab MeSH
- placeba MeSH
- protinádorové látky imunologicky aktivní MeSH
BACKGROUND: The role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery is not clear. METHODS: In a phase 3, multicenter, double-blind, randomized, controlled trial, we assigned patients with muscle-invasive urothelial carcinoma who had undergone radical surgery to receive, in a 1:1 ratio, either nivolumab (240 mg intravenously) or placebo every 2 weeks for up to 1 year. Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. The primary end points were disease-free survival among all the patients (intention-to-treat population) and among patients with a tumor programmed death ligand 1 (PD-L1) expression level of 1% or more. Survival free from recurrence outside the urothelial tract was a secondary end point. RESULTS: A total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. The median disease-free survival in the intention-to-treat population was 20.8 months (95% confidence interval [CI], 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to 13.9) with placebo. The percentage of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo (hazard ratio for disease recurrence or death, 0.70; 98.22% CI, 0.55 to 0.90; P<0.001). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 74.5% and 55.7%, respectively (hazard ratio, 0.55; 98.72% CI, 0.35 to 0.85; P<0.001). The median survival free from recurrence outside the urothelial tract in the intention-to-treat population was 22.9 months (95% CI, 19.2 to 33.4) with nivolumab and 13.7 months (95% CI, 8.4 to 20.3) with placebo. The percentage of patients who were alive and free from recurrence outside the urothelial tract at 6 months was 77.0% with nivolumab and 62.7% with placebo (hazard ratio for recurrence outside the urothelial tract or death, 0.72; 95% CI, 0.59 to 0.89). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 75.3% and 56.7%, respectively (hazard ratio, 0.55; 95% CI, 0.39 to 0.79). Treatment-related adverse events of grade 3 or higher occurred in 17.9% of the nivolumab group and 7.2% of the placebo group. Two treatment-related deaths due to pneumonitis were noted in the nivolumab group. CONCLUSIONS: In this trial involving patients with high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 274 ClinicalTrials.gov number, NCT02632409.).
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ClinicalTrials.gov
NCT02632409