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Conclusions: NIVO demonstrated a statistically significant and clinically meaningful improvement in DFS vs PBO for MIUC after radical surgery, both in ITT pts and pts with PD-L1 ≥ 1%. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 17.9% and 7.2% of pts in the NIVO and PBO arms, respectively. DFS improvement with NIVO was generally consistent across subgroups. DFS and NUTRFS were improved with NIVO vs PBO in both populations (Table).
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The primary endpoint of DFS was met in ITT pts (median follow-up, 20.9 mo for NIVO 19.5 mo for PBO) and in pts with PD-L1 ≥ 1%. Results: In total, 353 pts were randomized to NIVO (PD-L1 ≥ 1%, n = 140) and 356 pts to PBO (PD-L1 ≥ 1%, n = 142). Non–urothelial tract recurrence-free survival (NUTRFS) in ITT pts and in pts with PD-L ≥ 1% is a secondary endpoint. DFS was stratified by nodal status, prior neoadjuvant cisplatin, and PD-L1 status. Primary endpoints: disease-free survival (DFS) in all randomized pts (ITT population) and in pts with tumor PD-L1 expression ≥ 1%. Pts had radical surgery within 120 days ± neoadjuvant cisplatin or were ineligible/declined cisplatin-based chemo, evidence of UC at high risk of recurrence per pathologic staging, were disease-free by imaging, and ECOG PS ≤ 1. Pts were randomized 1:1 to NIVO 240 mg Q2W or PBO for ≤ 1 year of adjuvant treatment.
Checkmate 274 trial#
Methods: This is a phase 3, randomized, double-blind, multicenter trial of NIVO vs PBO in pts with high-risk MIUC (bladder, ureter, or renal pelvis) after radical surgery. This phase 3 trial of adjuvant nivolumab (NIVO) vs placebo (PBO) in pts with MIUC after radical surgery ± neoadjuvant cisplatin (CheckMate 274) aims to address an unmet need in these pts.
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There is no conclusive evidence supporting adjuvant chemo in pts who did not receive neoadjuvant chemo and in those with residual disease after neoadjuvant cisplatin.
![checkmate 274 checkmate 274](https://i.ytimg.com/vi/oC9iWUfRT-4/hqdefault.jpg)
This can bring a paradigm shift in the treatment of muscle-invasive urothelial carcinoma, by providing a therapeutic option to patients not eligible for cisplatin or in those with pathological evidence of residual disease despite neoadjuvant cisplatin-based chemotherapy.Ĭonflicts of interest: There are no conflicts of interest.Background: The standard of care (SOC) for patients (pts) with MIUC is radical surgery ± cisplatin-based neoadjuvant chemotherapy (chemo), but many pts are cisplatin-ineligible. , īased on Checkmate 274 trial, FDA has granted a priority review designation to nivolumab for use as adjuvant treatment in patients with surgically resected, high-risk, muscle-invasive urothelial carcinoma. However, DFS at 2–3 years is considered a surrogate of overall survival among patients with muscle-invasive urothelial carcinoma and thus, further follow-up may consolidate these findings by providing overall survival data. The secondary end point of overall survival was not achieved at the time of analysis, for which longer follow-up is required. About 48.2% of patients in the nivolumab arm and 57.3% of patients in the placebo group had disease recurrence or died during follow-up. The limitation of this trial is it being an interim analysis with a short follow-up of 20 months. The reason for this difference is also not clear however, this requires further analysis. Through a 1:1 randomization, nivolumab (240 mg) or placebo every 2 weeks was administered for up to 1 year or until disease recurrence or discontinuation from trial, with stratification according to tumor programmed death ligand-1 (PD-L1) expression level (≥1% vs. Patients included were those with Eastern Cooperative Oncology Group performance status score of 0 or 1 and who underwent radical surgery with pathological evidence of urothelial carcinoma (originating in the bladder, ureter, or renal pelvis) with or without neoadjuvant cisplatin-based chemotherapy with a high risk of recurrence (pT3, pT4a, or pN + and patient not eligible for, or declined, adjuvant cisplatin-based chemotherapy for patients who had not received neoadjuvant cisplatin-based chemotherapy and ypT2 to ypT4a or ypN + for patients who received neoadjuvant cisplatin. Available from: Ĭheckmate 274 is a phase 3, multicenter, double-blind, randomized controlled trial recently published in the New England Journal of Medicine, comparing nivolumab with placebo in adjuvant setting in patients with muscle-invasive urothelial carcinoma. Checkmate 274 trial: Is Nivolumab the new standard in adjuvant setting for high-risk muscle invasive urothelial carcinoma?.