Clinical trialPhase 3Bladder cancer

Adjuvant nivolumab versus placebo for high-risk muscle-invasive urothelial carcinoma: 5-year efficacy and ctDNA results from CheckMate 274

Annals of Oncology · 2026709 patients

Galsky M, Gschwend J, Milowsky M, Schenker M, Valderrama B, Tomita Y, et al. Annals of Oncology. 2026. 37:69-78

Study type: Clinical trial
Study name: CheckMate 274
Phase: Phase 3
Design: Multicentre, double-blind, placebo-controlled randomised trial (report with a minimum of 5 years of follow-up, with an exploratory post hoc ctDNA analysis)
Sample size: 709 patients
Source: Annals of Oncology · 2026

In plain words

In patients who had surgery for muscle-invasive bladder or urinary tract cancer and had a high risk of the cancer coming back, one year of the immunotherapy drug nivolumab after surgery lengthened the time without the cancer returning compared with a placebo (dummy treatment). This benefit was still seen after at least 5 years of follow-up, and no new side effects were reported. A ctDNA blood test (tracking tumour DNA) showed that patients with detectable ctDNA after surgery had a higher risk of the cancer coming back and gained the most from nivolumab; however, this finding still needs to be confirmed in further studies.

Key results

21.9 months (95% CI 18.8–36.9) with nivolumab vs 11.0 months (8.3–16.6) with placebo

Median DFS in all randomised patients

HR 0.74 (95% CI 0.61–0.90)

55.5 months (25.8–66.5) with nivolumab vs 8.4 months (5.6–20.0) with placebo

Median DFS in patients with tumour PD-L1 expression ≥1%

HR 0.58 (95% CI 0.42–0.79)

75.0 months (56.7–not estimable) with nivolumab vs 50.1 months (38.0–72.1) with placebo

Median OS in all randomised patients

HR 0.83 (95% CI 0.67–1.02)

54 patients (40.6%) of 133 evaluable patients

Detectable ctDNA at baseline (after radical surgery)

Exploratory post hoc analysis

52.1 months (19.4–not estimable) vs 5.0 months (2.8–6.5)

Median DFS by baseline ctDNA: undetectable vs detectable

HR 0.30 (95% CI 0.18–0.48)

0.35 (95% CI 0.18–0.66)

HR for disease-free survival, nivolumab vs placebo, in patients with detectable ctDNA

In patients included in the ctDNA analysis

0.99 (95% CI 0.51–1.93)

HR for disease-free survival, nivolumab vs placebo, in patients with undetectable ctDNA

In patients included in the ctDNA analysis

Drugs in this study:Nivolumab (Opdivo)

Dose and schedule cards

Adjuvant nivolumab (CheckMate 274)

High-risk invasive urothelial carcinoma within 120 days after radical surgery: ypT2 to ypT4a or ypN+ after neoadjuvant cisplatin; or pT3 to pT4a or pN+ without it in patients ineligible for or declining adjuvant cisplatinOn the page “Bladder cancer” · Muscle-invasive cancer (MIBC): after cystectomy (adjuvant)

Drug	Dose	Route	Schedule
Nivolumab	240 mg (or 480 mg)	IV infusion over 30 minutes	Every 2 weeks (480 mg: every 4 weeks)

Cycle length: Every 14 days (or 28 days)
Duration: Until recurrence or toxicity, up to 1 year

Per the FDA label and the CheckMate 274 trial. FDA approval applies regardless of PD-L1 expression, whereas EMA approval is limited to tumour-cell PD-L1 expression of 1% or higher.

On the page “Bladder cancer” · Muscle-invasive cancer (MIBC): after cystectomy (adjuvant)

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Nivolumab

Nivolumab 240 mg IV over 30 minutes every 2 weeks, for a maximum of 1 year or until recurrence or unacceptable toxicity. FDA-label equivalent: 240 mg every 2 weeks or 480 mg every 4 weeks for up to 1 year.

2Placebo

IV placebo over 30 minutes every 2 weeks, for a maximum of 1 year.

Source of the regimen details: Full text of the original report (PMC8215888) and the FDA label for OPDIVO (DailyMed)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

709 patients with muscle-invasive urothelial carcinoma (bladder, ureter or renal pelvis) who had undergone radical surgery with negative margins (R0) within 120 days before randomisation and were at high risk of recurrence: ypT2 to ypT4a or ypN+‎ after neoadjuvant cisplatin; or pT3 to pT4a or pN+‎ without neoadjuvant cisplatin in patients who were ineligible for or declined adjuvant cisplatin. ECOG 0 or 1; disease-free on imaging within 4 weeks before treatment; active autoimmune disease and HBV/HCV infection were exclusion criteria.

Endpoints

Primary endpoint: disease-free survival (DFS). Key secondary endpoint: overall survival (OS). In an exploratory post hoc analysis, baseline ctDNA was measured with the Signatera assay.

Safety and side effects

According to the abstract, no new safety signals were seen and the safety profile was consistent with previous reports. In the original report, treatment-related grade 3 or higher adverse events occurred in 17.9% with nivolumab vs 7.2% with placebo (most common: raised lipase 5.1% and amylase 3.7%); two treatment-related deaths due to pneumonitis.

Clinical significance and place in guidelines

This 5-year report confirms the durable DFS benefit of adjuvant nivolumab in high-risk MIUC after radical surgery and shows a stable safety profile. The OS improvement in the overall population was not statistically significant (HR 0.83, with a confidence interval including 1). The ctDNA analysis is exploratory and, according to the abstract, needs further validation before being used in clinical decision-making for patient selection. The status of drug approvals and clinical guideline recommendations should be checked separately, as they are not mentioned in the abstract.

Limitations

The ctDNA analysis was exploratory and post hoc and included only 133 evaluable patients. Confidence intervals in the subgroups are wide (for example HR 0.99 with a CI of 0.51–1.93 in undetectable ctDNA). The OS benefit in the overall population was not statistically significant. According to the authors, using ctDNA to tailor adjuvant therapy needs further validation.

Original article (DOI)PubMed

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.