CheckMate 274: 5-year data confirm durable benefit with nivolumab

Extended 5-year follow-up of the phase 3 CheckMate 274 study (NCT02632409) evaluating adjuvant nivolumab (Opdivo) in the treatment of high-risk muscle-invasive urothelial carcinoma found that the treatment continues to deliver gains in area such as disease-free survival (DFS) as well as median overall survival (OS) and disease-specific survival (DSS), according to data presented at the 2025 European Society for Medical Oncology Congress in Berlin, Germany.¹

Presenting author Matthew D. Galsky, MD, director of GU medical oncology at the Icahn School of Medicine at Mount Sinai and the associate director for translational research at the Tisch Cancer Institute in New York, New York, explained that CheckMate 274 met its primary end points of disease-free survival in both the intent-to-treat population as well as in patients with PD-L1 expression of 1% or greater.² Additionally, 36.1-month follow-up data pointed to the efficacy of the treatment, and interim OS also favored nivolumab.³ At ESMO 2025, Galsky presented CheckMate 274 data reflecting 5-year minimum follow-up as well as exploratory ctDNA data.

The randomized, double-blind, multicenter CheckMate 274 study evaluated patients with ypT2-ypT4a or ypN+ muscle-invasive urothelial carcinoma who received neoadjuvant cisplatin chemotherapy, patients with pT3-pT4a or pN+ muscle-invasive urothelial carcinoma without prior neoadjuvant cisplatin chemotherapy and not eligible/refused adjuvant cisplatin chemotherapy, patients who had received radical surgery within the previous 120 days, and patients with disease-free status within 4 weeks of randomization. A total of 709 patients were randomly assigned 1:1 to receive either intravenous nivolumab 240 mg once every 2 weeks or intravenous placebo once every 2 weeks. Primary end points were DFS in all patients who were randomly assigned and in all patients who were randomly assigned and had tumor PD-L1 expression of at least 1%. Secondary end points included OS and DSS, and safety was an exploratory end point.

Galsky reported that the median 5-year DFS for all randomly assigned patients in the niuvolumab group was 21.9 months (95% CI: 18.8-36.9) vs 11.0 months (95% CI: 8.3-16.6) in patients receiving placebo (HR, 0.74, 95% CI: 0.61-0.90).

For patients with PD-L1 expression of 1% or greater, median DFS was 55.5 months (95% CI: 25.8-66.5) in the nivolumab group vs 8.4 months (95% CI: 5.6-20.0) in the placebo group (HR, 0.58, 95% CI: 0.42-0.79). In randomly assigned patients who had muscle-invasive bladder cancer (MIBC), median DFS was 25.6 months (95% CI: 19.2-24.6) in the nivolumab group and 9.4 months in the placebo group (95% CI: 7.4-13.7) (HR, 0.66, 95% CI: 0.53-0.81). In patients with MIBC who had PD-L1 expression of 1% or greater, median DFS was 59.4 months (39.5-NE) in the nivolumab group and 8.3 months (95% CI: 4.7-16.6) in the placebo group (HR, 0.50, 95% CI: 0.36-0.72).

The investigators also evaluated outcomes in patients with MIBC by prior neoadjuvant chemotherapy status. In all randomly assigned patients with MIBC who had received prior cisplatin, median DFS was 19.5 months (95% CI: 15.6-48.2) in the nivolumab group and 8.3 months (95% CI: 5.6-11.2) in the placebo group (HR, 0.63, 95% CI: 0.47-0.84). For randomly assigned patients with MIBC who had not received prior cisplatin, median DFS was 25.9 months (95% CI: 19.2-55.5) in the nivolumab group vs 13.7 months (95% CI: 8.2-22.1) in the placebo group (HR, 0.70, 95% CI: 0.52-0.95).

“With 5 years of follow-up, median overall survival is longer with nivolumab vs placebo on interim analysis. In all randomized patients, the median overall survival is 75 months with nivolumab and 50.1 months with placebo, with a hazard ratio of 0.83. In patients with tumor PD-L1 greater than or equal to 1%, the median OS with nivolumab is not reached, and the median OS with placebo is 59.4 months, with a hazard ratio of 0.63, Galsky reported.

In randomly assigned patients with MIBC, interim median OS was 61.2 months (95% CI: 48.2-NE) in the nivolumab group vs 38.2 months (95% CI: 29.8-50.3) in the placebo group (HR, 0.73: 0.58-0.91). In patients with MIBC and PD-L1 expression of at least 1%, interim median OS was not reached (95% CI: 75.0-NE) in the nivolumab group and 38.2 months (95% CI: 27.8-72.1) in the placebo group (HR, 0.51, 95% CI: 0.35-0.76).

Regarding DSS, “Disease-specific survival was longer with nivolumab vs placebo. In all randomized patients, the hazard ratio was 0.79. In patients with tumor PD-L1 greater than or equal to 1%, the hazard ratio was 0.57,” Galsky said.

The investigators performed ctDNA analysis on 133 of the 709 randomly assigned patients (18.8%); of these, 54 (40.6%) had detectable ctDNA. Median DFS was 52.1 months (95% CI: 19.4-NE) in patients with undetectable ctDNA vs 5.0 months (95% CI: 2.8-6.5) in patients with detectable ctDNA (HR, 0.30, 95% CI: 0.18-0.48). Median OS was not reached (95% CI: 62.0-NE) in patients with undetectable ctDNA vs 28.2 months (95% CI: 19.4-36.1) in patients with detectable ctDNA (HR, 0.44, 95% CI: 0.25-0.76).

When stratified by treatment arm, patients in the nivolumab group with detectable ctDNA had a median DFS of 7.4 months (95% CI: 2.8-19.2) vs 2.8 months (95% CI: 2.4-5.0) in the placebo group (HR, 0.35, 95% CI: 0.18-0.66). Patients in the nivolumab group with undetectable ctDNA had a median DFS of 91.9 months (95% CI:19.2-NE) vs 52.2 months (16.9-NE) in the placebo group (HR, 0.99, 95% CI: 0.51-1.93). Median OS in patients with detectable ctDNA receiving nivolumab was 36.2 months (95% CI: 23.0-NE) vs 19.3 months (95% CI: 8.1-28.2) in the placebo group. In patients with undetectable ctDNA, median OS was not reached (95% CI, 62.0-NE) in the nivolumab group vs not reached (95% CI: 40.7-NE) in the placebo group (HR, 0.87, 95% CI: 0.41-1.84).

In terms of safety, “Importantly, no new safety signals have emerged, and at this time, all patients have been off treatment for more than 4 years,” Galsky said.

In all, Galsky said the results presented at ESMO 2025 “provide additional support for adjuvant nivolumab as a standard treatment for patients with high-risk muscle-invasive urothelial cancer after radical surgery.”

DISCLOSURES: Galsky noted advisory board/consulting disclosures with AbbVie, Alligator Bioscience, Analog Devices, ARS Pharmaceuticals, Asieris Pharmaceuticals, AstraZeneca, Basilea Pharmaceutica, Bicycle Therapeutics, Bristol Myers Squibb, Curis, Daiichi Sankyo, Dragonfly Therapeutics, EMD Serono, Fujifilm, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Numab Therapeutics, Pfizer, Rappta Therapeutics, Seagen, UroGen Pharma, and Veracyte.

REFERENCES

1. Galsky MD, Gscwhend J, Milowsky M, et al. Adjuvant nivolumab vs placebo for high-risk muscle-invasive urothelial carcinoma: 5-year efficacy and ctDNA results from CheckMate 274. Presented at: European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. Abstract 3068O. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2025_abstracts/3068O.html.pdf

2. Bajorin DF, Witjes A, Gschwen JE, et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med. 2021;384:2102-2114. doi:10.1056/NEJMoa2034442

3. Galsky MD, Witjes JA, Gschwend JE, et al. Adjuvant nivolumab in high-risk muscle-invasive urothelial carcinoma: Expanded efficacy from CheckMate 274. J Clin Oncol. 2025;43(1):15-21. doi:10.1200/JCO.24.00340