TY - JOUR
T1 - Disease-free Survival Analysis for Patients with High-risk Muscle-invasive Urothelial Carcinoma from the Randomized CheckMate 274 Trial by PD-L1 Combined Positive Score and Tumor Cell Score
AU - Galsky, Matthew D.
AU - Bajorin, Dean F.
AU - Witjes, Johannes Alfred
AU - Gschwend, Jürgen E.
AU - Tomita, Yoshihiko
AU - Nasroulah, Federico
AU - Li, Jun
AU - Collette, Sandra
AU - Valderrama, Begoña P.
AU - Grimm, Marc Oliver
AU - Appleman, Leonard
AU - Gravis, Gwenaelle
AU - Necchi, Andrea
AU - Ye, Dingwei
AU - Stenner, Frank
AU - Wind-Rotolo, Megan
AU - Zhang, Joshua
AU - Ünsal-Kaçmaz, Keziban
N1 - Publisher Copyright:
© 2023 The Author(s)
PY - 2023/5
Y1 - 2023/5
N2 - Background: 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%. Objective: To analyze DFS by combined positive score (CPS), which is based on PD-L1 expression in both tumor and immune cells. Design, setting, and participants: 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. Intervention: Nivolumab 240 mg. Outcome measurements and statistical analysis: 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. Results and limitations: 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). Conclusion: 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. Patient summary: 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.
AB - Background: 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%. Objective: To analyze DFS by combined positive score (CPS), which is based on PD-L1 expression in both tumor and immune cells. Design, setting, and participants: 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. Intervention: Nivolumab 240 mg. Outcome measurements and statistical analysis: 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. Results and limitations: 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). Conclusion: 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. Patient summary: 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.
KW - CheckMate 274
KW - Combined positive score
KW - Nivolumab
KW - PD-L1 expression
UR - http://www.scopus.com/inward/record.url?scp=85150455142&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2023.01.016
DO - 10.1016/j.eururo.2023.01.016
M3 - Article
C2 - 36868932
AN - SCOPUS:85150455142
SN - 0302-2838
VL - 83
SP - 432
EP - 440
JO - European Urology
JF - European Urology
IS - 5
ER -