Despite surgery, recurrence rates remain high in muscle-invasive urothelial carcinoma (MIUC). The phase III randomized, double-blind, multicenter CheckMate 274 trial comparing adjuvant nivolumab versus placebo in patients with high-risk MIUC after radical surgery demonstrated that adjuvant nivolumab improved disease-free survival (DFS) versus placebo.
We report results with 5-year minimum follow-up including exploratory analyses of circulating tumor DNA (ctDNA).
Eligible patients had radical surgery (R0, with negative surgical margins) within 120 days before randomization, with or without neoadjuvant cisplatin-based chemotherapy. Overall, 709 patients with MIUC at high risk of recurrence after surgery were randomized 1:1 to nivolumab 240 mg or placebo every 2 weeks for ≤1 year. The primary endpoint was DFS. Overall survival (OS) was a key secondary endpoint. In a post-hoc exploratory analysis, baseline ctDNA was measured using the Signatera assay.
Median DFS was 21.9 (95% CI 18.8-36.9) months with nivolumab versus 11.0 (95% CI 8.3-16.6) months with placebo in all-randomized patients (HR [95% CI] 0.74 [0.61-0.90]), and 55.5 (95% CI 25.8-66.5) months versus 8.4 (95% CI 5.6-20.0) months in patients with tumor programmed death ligand 1 expression ≥1% (HR [95% CI] 0.58 [0.42-0.79]). In all randomized patients, median OS was 75.0 (95% CI 56.7-not estimable) months with nivolumab versus 50.1 (95% CI 38.0-72.1) months with placebo (HR, 0.83 [95% CI 0.67-1.02]). Baseline ctDNA post-radical surgery was detected in 54 (40.6%) of 133 evaluable patients. Median DFS was 52.1 (19.4-not estimable) months versus 5.0 (2.8-6.5) months in patients with undetectable versus detectable ctDNA at baseline (HR [95% CI], 0.30 [0.18-0.48]). In patients included in the ctDNA analysis who had detectable ctDNA, the median DFS HR (95% CI) for nivolumab-treated patients versus placebo-treated patients was 0.35 (0.18-0.66), while in patients with undetectable ctDNA, the HR (95% CI) for nivolumab-treated patients versus with placebo-treated patients was 0.99 (0.51-1.93). There were no new safety signals.
Five-year results confirm durable DFS benefit and consistent safety profile for adjuvant nivolumab in high-risk MIUC. Post-hoc exploratory ctDNA assessment identified patients at highest risk of recurrence and may inform tailored adjuvant therapy strategies, pending further validation.
Annals of oncology : official journal of the European Society for Medical Oncology. 2025 Oct 17 [Epub ahead of print]
M D Galsky, J E Gschwend, M I Milowsky, M Schenker, B P Valderrama, Y Tomita, A Bamias, T Lebret, S F Shariat, S H Park, M Agerbaek, G Jha, F Stenner, D Ye, F Giudici, J Connors, S Gupta, A Chhibber, J Zhang, D F Bajorin, J A Witjes
Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: ., Technical University Munich, Munich, Germany., University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA., Sf. Nectarie Oncology Center, Craiova, Romania., Hospital Universitario Virgen del Rocío, Sevilla, Spain., Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan., National and Kapodistrian University of Athens, Athens, Greece., Hôpital Foch, Paris-Saclay University UVSQ, Versailles, France., Medical University of Vienna, Vienna General Hospital, Vienna, Austria., Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea., Aarhus University Hospital, Aarhus, Denmark., M Health Fairview Clinics and Surgery Center, Minneapolis, MN, USA., University Hospital Basel, Basel, Switzerland., Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, China., Global Biometric & Data Sciences, Bristol Myers Squibb, Boudry, Switzerland., Global Drug Development, Bristol Myers Squibb, Princeton, NJ, USA., Translational Medicine Oncology, Bristol Myers Squibb, Princeton, NJ, USA., Oncology Clinical Development, Bristol Myers Squibb, Princeton, NJ, USA., Memorial Sloan Kettering Cancer Center, New York, NY, USA., Radboud University, Nijmegen, the Netherlands.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/41110694