Adjuvant Nivolumab Improves DFS and Shows Favorable OS Trends in High-Risk MIUC: CheckMate 274 Update

The phase III CheckMate 274 trial demonstrated that adjuvant nivolumab offers a significant and clinically meaningful improvement in disease-free survival (DFS) compared with placebo for patients with high-risk muscle-invasive urothelial carcinoma (MIUC) after radical surgery (RS), with or without prior neoadjuvant cisplatin-based chemotherapy (NAC).

After a median follow-up of three years in the trial, nivolumab continued to show an improvement in DFS compared with placebo in primary efficacy populations, including intent-to-treat (ITT) patients and patients with tumor programmed cell death ligand 1 (PD-L1) expression ≥ 1%, as well as those with muscle-invasive bladder cancer (MIBC). An early interim analysis also showed trends favoring nivolumab over placebo for overall survival (OS) in both ITT and tumor PD-L1 expression ≥ 1% populations.

Additional efficacy outcomes for patients with MIBC were reported at the American Society of Clinical Oncology 2025 Genitourinary Cancers Symposium.

A total of 709 patients were randomized 1:1 to receive 240 mg of nivolumab every two weeks or placebo for one year or less of adjuvant treatment, grouped by tumor PD-L1 expression, nodal status, and prior NAC.

The primary endpoints were DFS in the ITT population and DFS in patients with tumor PD-L1 expression ≥ 1%. The OS in the ITT population and patients with tumor PD-L1 expression ≥ 1% was a secondary endpoint, and analysis of patients with MIBC was exploratory. Preplanned interim analyses provided MIBC OS data for the ITT population and patients with tumor PD-L1 expression ≥ 1%, but OS follow-up remains ongoing because statistical significance thresholds were not met at the time of analysis.

Of 560 (79%) patients with MIBC (nivolumab, n=279; placebo, n=281), 284 (51%) had prior NAC. The median follow-up was 36.1 months (ITT). DFS improvement with nivolumab over placebo was observed across all patients with MIBC (hazard ratio [HR], 0.63) and in those with (HR, 0.58) and without prior NAC (HR, 0.69). For OS, HRs favored nivolumab over placebo in all patients with MIBC (HR, 0.70) and the tumor PD-L1 ≥ 1% subgroup (HR, 0.48), as well as in patients with MIBC with (HR, 0.74) and without prior NAC (HR, 0.67). The safety profile remained consistent with previous data, and no new safety concerns were identified.

With a median follow-up of three years, nivolumab demonstrated sustained DFS benefits across all patients with MIBC and in prior NAC subgroups. Since OS trends consistently favored nivolumab, these data reinforce nivolumab’s role as an adjuvant standard of care for high-risk MIUC and MIBC, with the potential for curative outcomes.