Nivolumab is a fully human IgG4 monoclonal antibody directed against programmed death 1. 1, 2, 6- 9 Furthermore, despite a high risk of metastatic recurrence, no standard adjuvant systemic therapies have been shown to improve outcomes in patients with pathological evidence of residual disease after neoadjuvant cisplatin-based chemotherapy. 1- 4 Adjuvant chemotherapy may prolong disease-free survival among patients with locally advanced upper tract urothelial carcinoma, 5 but no consensus has emerged regarding routine adjuvant cisplatin-based chemotherapy, and some patients with urothelial carcinoma are ineligible for or decline neoadjuvant cisplatin-based chemotherapy. 1, 2 Although radical surgery is performed with curative intent, more than 50% of patients with pathological evidence of cancer invading through the muscularis propria or involving the regional lymph nodes will have lethal metastatic recurrence. Radical surgery involving cystectomy for tumors arising in the bladder or nephroureterectomy for tumors arising in the upper urinary tract is the standard of care for patients with muscle-invasive urothelial carcinoma. Two treatment-related deaths due to pneumonitis were noted in the nivolumab group. Treatment-related adverse events of grade 3 or higher occurred in 17.9% of the nivolumab group and 7.2% of the placebo group. 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).
CHECKMATE 274 FREE
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). 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. 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 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). The median disease-free survival in the intention-to-treat population was 20.8 months (95% confidence interval, 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to 13.9) with placebo. (Funded by Bristol Myers Squibb and Ono Pharmaceutical CheckMate 274 number, NCT02632409.).Ī total of 353 patients were assigned to receive nivolumab and 356 to receive placebo.
CHECKMATE 274 TRIAL
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 PConclusionsIn 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.
Survival free from recurrence outside the urothelial tract was a secondary end point.ResultsA total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. 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.
Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. BackgroundThe role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery is not clear.MethodsIn 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.
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