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

作者：Matthew D. Galsky, Jürgen E. Gschwend, Matthew I. Milowsky, Michael Schenker, Begoña P. Valderrama, Yoshihiko Tomita, Aristotelis Bamias, Thierry Lebrét, Shahrokh F. Shariat, Se Hoon Park, Mads Agerbæk, Gautam Jha, Frank Stenner, Dingwei Ye, Fabio Giudici, Jessica Connors, Shilpa Gupta, Aparna Chhibber, J. Zhang, Dean F. Bajorin, J. Alfred Witjes · 发表于：Annals of Oncology · 年份：2025 · DOI：10.1016/j.annonc.2025.09.139 · 被引用次数：33 · 研究领域：Bladder and Urothelial Cancer Treatments、Cancer Immunotherapy and Biomarkers、Esophageal Cancer Research and Treatment

BACKGROUND: 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). PATIENTS AND METHODS: Eligible patients had radical surgery (R0, with negative surgical margins) within 120 days before being randomized, with or without neoadjuvant cisplatin-based chemotherapy. Overall, 709 patients with MIUC at high risk of recurrence after surgery were randomly assigned 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. RESULTS: Median DFS was 21.9 months [95% confidence interval (CI) 18.8-36.9 months] with nivolumab versus 11.0 months (95% CI 8.3-16.6 months) with placebo in all randomized patients [hazard ratio (HR) 0.74, 95% CI 0.61-0.90], and 55.5 months (95% CI 25.8-66.5 months) versus 8.4 months (95% CI 5.6-20.0 months) in patients with tumor programmed death-ligand 1 expression ≥1% (HR 0.58, 95% CI 0.42-0.79). In all randomized patients, median OS was 75.0 months (95% CI 56.7 months-not estimable) ...