基于 PD-L1 联合阳性评分和肿瘤细胞评分的随机 CheckMate 274 试验中高危肌肉浸润性尿路上皮癌患者的无病生存分析。
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.
机构信息
Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
出版信息
Eur Urol. 2023 May;83(5):432-440. doi: 10.1016/j.eururo.2023.01.016. Epub 2023 Mar 2.
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.
背景
CheckMate 274 试验表明，在根治性手术后有高复发风险的肌层浸润性尿路上皮癌患者中，与安慰剂相比，接受辅助纳武利尤单抗治疗可改善无病生存期（DFS）。该试验的人群为意向治疗人群和肿瘤程序性死亡配体 1（PD-L1）表达≥1%亚组患者。
目的
通过基于肿瘤和免疫细胞中 PD-L1 表达的组合阳性评分（CPS）来分析 DFS。
设计、地点和参与者：我们将总共 709 例患者以 1:1 的比例随机分配，接受纳武利尤单抗 240mg 或安慰剂，每 2 周静脉输注一次，最长不超过 1 年的辅助治疗。
干预措施
纳武利尤单抗 240mg。
结局测量和统计分析
主要终点是意向治疗人群和肿瘤 PD-L1 表达≥1%患者的 DFS，使用肿瘤细胞（TC）评分。CPS 是从先前染色的切片中回顾性确定的。对同时具有可量化 CPS 和 TC 的肿瘤样本进行分析。
结果和局限性
在可评估 CPS 和 TC 的 629 例患者中，557 例（89%）有 CPS≥1，72 例（11%）有 CPS<1，249 例（40%）有 TC≥1%，380 例（60%）有 TC<1%。在 TC<1%的患者中，81%（n=309）有 CPS≥1。与安慰剂相比，纳武利尤单抗可改善 TC≥1%的患者（风险比[HR]0.50，95%置信区间[CI]0.35-0.71）、CPS≥1 的患者（HR 0.62，95%CI 0.49-0.78）以及 TC<1%和 CPS≥1 的患者（HR 0.73，95%CI 0.54-0.99）的 DFS。
结论
CPS≥1 的患者多于 TC≥1%的患者，而且大多数 TC<1%的患者有 CPS≥1。此外，CPS≥1 的患者接受纳武利尤单抗治疗可改善 DFS。这些结果可能部分解释了即使 TC<1%和 CPS≥1 的患者接受辅助纳武利尤单抗治疗也能获益的机制。
患者总结
我们在 CheckMate 274 试验中研究了接受手术后（膀胱癌患者切除膀胱或泌尿道部分）接受纳武利尤单抗与安慰剂治疗的患者无癌症复发（无病生存期；DFS）时间。我们评估了蛋白 PD-L1 在肿瘤细胞（肿瘤细胞评分；TC）上或在肿瘤周围的肿瘤细胞和免疫细胞上（组合阳性评分；CPS）的表达水平的影响。与安慰剂相比，纳武利尤单抗可改善 TC≥1%、CPS≥1%和 TC<1%且 CPS≥1%的患者的 DFS。这项分析可能有助于医生了解哪些患者最受益于纳武利尤单抗治疗。
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