The CheckMate 274 trial demonstrated improved disease-free survival (DFS) with adjuvant nivolumab versus placebo in patients with muscle-invasive urothelial carcinoma at high risk of recurrence after radical surgery in both the intent-to-treat population and the subset with tumor programmed death ligand 1 (PD-L1) expression ≥1%.
To analyze DFS by combined positive score (CPS), which is based on PD-L1 expression in both tumor and immune cells.
We randomized a total of 709 patients 1:1 to nivolumab 240 mg or placebo every 2 wk intravenously for ≤1 yr of adjuvant treatment.
Nivolumab 240 mg.
Primary endpoints were DFS in the intent-to-treat population and patients with tumor PD-L1 expression ≥1% using the tumor cell (TC) score. CPS was determined retrospectively from previously stained slides. Tumor samples with both quantifiable CPS and TC were analyzed.
Of 629 patients evaluable for CPS and TC, 557 (89%) had CPS ≥1, 72 (11%) had CPS <1, 249 (40%) had TC ≥1%, and 380 (60%) had TC <1%. Among patients with TC <1%, 81% (n = 309) had CPS ≥1. DFS was improved with nivolumab versus placebo for patients with TC ≥1% (hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.35-0.71), those with CPS ≥1 (HR 0.62, 95% CI 0.49-0.78), and patients with both TC <1% and CPS ≥1 (HR 0.73, 95% CI 0.54-0.99).
More patients had CPS ≥1 than TC ≥1%, and most patients who had TC <1% had CPS ≥1. In addition, patients with CPS ≥1 experienced improved DFS with nivolumab. These results may, in part, explain the mechanisms underlying a benefit with adjuvant nivolumab even in patients who had both TC <1% and CPS ≥1.
We studied survival time without cancer recurrence (disease-free survival; DFS) for patients treated with nivolumab versus placebo after surgery to remove the bladder or components of the urinary tract for bladder cancer in the CheckMate 274 trial. We assessed the impact of levels of the protein PD-L1 expressed either on tumor cells (tumor cell score; TC) or on both tumor cells and immune cells surrounding the tumor (combined positive score; CPS). DFS was impoved with nivolumab versus placebo for patients with TC ≥1%, CPS ≥1, and for patients with both TC <1% and CPS ≥1. This analysis may help physicians understand which patients would benefit most from treatment with nivolumab.
European urology. 2023 Mar 01 [Epub ahead of print]
Matthew D Galsky, Dean F Bajorin, Johannes Alfred Witjes, Jürgen E Gschwend, Yoshihiko Tomita, Federico Nasroulah, Jun Li, Sandra Collette, Begoña P Valderrama, Marc-Oliver Grimm, Leonard Appleman, Gwenaelle Gravis, Andrea Necchi, Dingwei Ye, Frank Stenner, Megan Wind-Rotolo, Joshua Zhang, Keziban Ünsal-Kaçmaz
Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: ., Memorial Sloan Kettering Cancer Center, New York, NY, USA., Radboud University, Nijmegen, The Netherlands., Technical University Munich, Munich, Germany., Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan., Bristol Myers Squibb, Princeton, NJ, USA., Bristol Myers Squibb, Brussels, Belgium., Hospital Universitario Virgen del Rocío, Sevilla, Spain., Jena University Hospital, Jena, Germany., University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA., Institut Paoli-Calmettes Aix-Marseille Université, Marseille, France., Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Fudan University Shanghai Cancer Center, Shanghai, China., University Hospital Basel, Basel, Switzerland.